Publications by authors named "Narsis Daftarian"

47 Publications

Application of a Mapping Method in the Analysis of Electroretinogram in Patients with Retinitis Pigmentosa.

Semin Ophthalmol 2021 Sep 9:1-7. Epub 2021 Sep 9.

Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: Retinitis pigmentosa (RP) is a group of degenerative retinal diseases characterized by mutations in genes affecting retinal pigment epithelium (RPE) function, as well as mutations directly involving photoreceptors. This paper aims to evaluate a nonlinear method to distinguish between the RP and normal eye based on the Electroretinogram (ERG) signal.

Method: ERG signal was recorded from 28 eyes of patients with the RP and 32 normal eyes. The ERG signal consists of four different stimuli, including two dark-adapted and two light-adapted stimuli. The time-domain analysis includes the amplitude and implicit time to consider the robustness of the nonlinear method. A parabolic mapping method was performed, and two criteria (Theta angle and density) extracted from the parabola were compared for both groups.

Results: The results showed that a-wave's amplitude and implicit time significantly changed in the dark- and light-adapted stimuli. The amplitude of the b-wave showed significant changes in all stimuli. However, the implicit time of b-wave had a significant increase only in the dark-adapted 3.0 ERG. Both nonlinear criteria showed significant changes in the RP group for all the stimuli. The -values of dark-adapted 3.0 (.0121), dark-adapted 10.0 (.0014), light-adapted 3.0 (.0119), and flicker 30 Hz (.0323) showed significant differences. Using the density criterion, the statistical test demonstrated a significant difference between the RP and healthy normal group in dark-adapted 3.0 (.0076), dark-adapted 10.0 (.0024), light-adapted 3.0 (.0021), and flicker 30 Hz (.0165).

Conclusion: The proposed features have made it possible to distinguish between healthy and RP eyes. This method might be helpful in early diagnosis.
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http://dx.doi.org/10.1080/08820538.2021.1967411DOI Listing
September 2021

Retinal Vascular Abnormalities in Different Types of Inherited Retinal Dystrophies Assessed by Optical Coherence Tomography Angiography.

J Curr Ophthalmol 2021 Apr-Jun;33(2):189-196. Epub 2021 Jul 5.

Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: To investigate the retinal vascular characteristics among patients with different types of inherited retinal dystrophies (IRDs).

Methods: This comparative cross-sectional study was conducted on 59 genetically confirmed cases of IRD including 37 patients with retinitis pigmentosa (RP) (74 eyes), 13 patients with Stargardt disease (STGD) (26 eyes), and 9 patients with cone-rod dystrophy (CRD) (18 eyes). Both eyes of 50 age- and sex-matched healthy individuals were investigated as controls. All participants underwent optical coherence tomography angiography to investigate the vascular densities (VDs) of superficial and deep capillary plexus (SCP and DCP) as well as foveal avascular zone area.

Results: In RP, significantly lower VD in whole image ( = 0.001 for DCP), fovea ( = 0.038 for SCP), parafovea ( < 0.001 for SCP and DCP), and perifovea ( < 0.001 for SCP and DCP) was observed compared to controls. In STGD, VD of parafovea ( = 0.012 for SCP and = 0.001 for DCP) and fovea ( = 0.016 for DCP) was significantly lower than controls. In CRD, the VD of parafovea ( = 0.025 for DCP) was significantly lower than controls. Whole image density was significantly lower in RP compared to STGD ( < 0.001 for SCP) and CRD ( = 0.037 for SCP). VD in parafovea ( = 0.005 for SCP) and perifovea ( < 0.001 for SCP and DCP) regions was significantly lower in RP compared with STGD. Also, foveal VD in STGD was significantly lower than RP ( = 0.023 for DCP).

Conclusion: Our study demonstrated lower VDs in three different IRDs including RP, STGD, and CRD compared to healthy controls. Changes were more dominant in RP patients.
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http://dx.doi.org/10.4103/joco.joco_11_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365577PMC
July 2021

New criteria for evaluation of electroretinogram in patients with retinitis pigmentosa.

Doc Ophthalmol 2021 Jun 30. Epub 2021 Jun 30.

Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Electroretinogram (ERG) plays an essential role in the diagnosis of retinal disease. Choosing appropriate methods could extract valuable information from ERG. In this study, a new criterion based on time-frequency domain analysis was proposed to investigate the retina in retinitis pigmentosa (RP) patients.

Materials And Methods: The total number of 16 eyes from eight RP patients and 20 eyes from age-matched healthy subjects were assessed. The signals included photopic and scotopic ERGs. Continuous wavelet transform was applied to ERGs. Dominant frequencies were extracted, and the contours related to these dominant frequencies were selected. As a new criterion, the areas related to dominant frequency contours were considered a feature to differentiate the RP and normal groups. To better evaluate the proposed criterion results, the time-domain analysis characteristics of ERG were also considered.

Results: The results showed an increase in implicit time and reduced amplitude in RP patients (P < 0.05). A significant decrease of dominant frequencies and increasing their occurrence time were seen in ERG of RP patients. Also, in RP patients, the third dominant frequency was disappeared from the three main frequencies observed in photopic ERGs of normal subjects. The area criterion showed a significant decrease in RP groups (P < 0.05).

Conclusion: RP can cause changes in the time and time-frequency components of the ERG. The area index could represent a new view of the characteristics of the ERG in the time-frequency domain. This criterion can help the ophthalmologist to have a better evaluation of retinal disease.
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http://dx.doi.org/10.1007/s10633-021-09843-xDOI Listing
June 2021

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.

Hum Genet 2021 Jun 20. Epub 2021 Jun 20.

Institute of Human Genetics, Julius Maximilians University Würzburg, 97074, Würzburg, Germany.

Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.
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http://dx.doi.org/10.1007/s00439-021-02303-1DOI Listing
June 2021

Intravitreal connective tissue growth factor neutralizing antibody or bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model.

Exp Eye Res 2021 07 19;208:108622. Epub 2021 May 19.

Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Connective tissue growth factor (CTGF) is released by retinal pigment epithelial (RPE) cells and detectable in proliferative membranes (PrMs). This experimental study was performed to investigate the mRNA and protein levels of both CTGF and vascular endothelial growth factor A (VEGF-A) in a rabbit model of proliferative vitreoretinopathy (PVR). In addition, the effects of a single intravitreal injection of the safe dose of anti-CTGF or bevacizumab as monotherapy and in combination were evaluated. PVR was induced in the right eye of albino rabbits by intravitreal injection of cultured adult human RPE cells. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot analysis of CTGF and VEGF-A were performed on whole eye tissue in the PVR model versus controls at different time points. In the next step, the PVR models were assigned to five groups. The monotherapy groups received a single intravitreal injection of 0.1 ml of anti-CTGF 100 μg/ml (final concentration of 6.6 μg/ml in the vitreous) or 0.03 ml of 25 mg/ml bevacizumab. In the combined group, the abovementioned amounts of anti-CTGF and bevacizumab were injected intravitreally from separate sites in one session. No antibody injection was performed in the control group. Intravitreal injection of 0.1 ml of control IgG (1 mg/ml of isotype matched) antibody was performed in the placebo group. After 2 weeks, histologic evaluation including, trichrome staining for collagen, immunostaining by anti-alpha-smooth muscle actin for myofibroblasts, and anti-collagen type-1 antibody on paraffin embedded anterior-posterior sections was done. In addition, fundus photography was performed for clinically equivalent PVR staging. Twenty-four hours following PVR induction, CTGF mRNA and protein levels increased five- and- three-fold compared to controls, respectively (P < 0.001). VEGF-A mRNA and protein levels decreased significantly after 72 h of PVR induction compared to controls (P < 0.05). Means of PrM thickness and myofibroblast cell counts significantly decreased in the anti-CTGF group (P < 0.001 and P < 0.05, respectively). The mean area of collagen type-1 fibers of PrM in the mono- and combination therapy groups that received intravitreal anti-CTGF was significantly reduced (P < 0.001); in addition, mild PVR (stage-1 and 2) formation occurred in comparison with moderate to severe PVR (stage-4 and higher) in other groups. In conclusion, we found that intravitreal injection of CTGF neutralizing antibody resulted in a reduction in PrM thickness, collagen fibers and myofibroblast density in the PVR model. CTGF inhibition may represent a potential therapeutic target for PVR.
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http://dx.doi.org/10.1016/j.exer.2021.108622DOI Listing
July 2021

Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.

J Ophthalmol 2021 30;2021:6674290. Epub 2021 Apr 30.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: To describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series.

Methods: Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients.

Results: The age at onset was 4-35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies.

Conclusions: ARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB.
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http://dx.doi.org/10.1155/2021/6674290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105111PMC
April 2021

Choroidal Thickness in Different Types of Inherited Retinal Dystrophies.

J Ophthalmic Vis Res 2020 Jul-Sep;15(3):351-361. Epub 2020 Aug 6.

Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: To compare the choroidal thickness among eyes with retinitis pigmentosa (RP), Stargardt disease, Usher syndrome, cone-rod dystrophy, and healthy eyes of sex- and age-matched individuals.

Methods: In this comparative study, 503 eyes with RP ( = 264), cone-rod dystrophy ( = 109), Stargardt disease ( = 76), and Usher syndrome ( = 54) were included. To validate the data, 109 healthy eyes of 56 sex- and age-matched individuals were studied as controls. Choroidal imaging was performed using enhanced depth imaging-optical coherence tomography. Choroidal thickness was measured manually using MATLAB software at 13 points in nasal and temporal directions from the foveal center with the interval of 500 µm and the choroidal area encompassing the measured points was calculated automatically.

Results: The mean age was 36.33 13.07 years (range, 5 to 72 years). The mean choroidal thickness at 13 points of the control eyes was statistically significantly higher than that in eyes with RP ( 0.001) and Usher syndrome ( 0.05), but not significantly different from that in eyes with Stargardt disease and cone-rod dystrophy. Among different inherited retinal dystrophies (IRDs), the choroidal thickness was the lowest in eyes with RP ( 0.001). Choroidal thickness in the subfoveal area correlated negatively with best-corrected visual acuity ( = 0.264, 0.001) and the duration of ocular symptoms ( = 0.341, 0.001) in all studied IRDs. No significant correlation was observed between the subfoveal choroidal thickness and central macular thickness ( = 0.24, = 0.576).

Conclusion: Choroidal thinning in four different types of IRDs does not follow a similar pattern and depends on the type of IRD and the duration of ocular symptoms. A larger cohort is required to verify these findings.
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http://dx.doi.org/10.18502/jovr.v15i3.7454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431727PMC
August 2020

A lab-on-a-chip model of glaucoma.

Brain Behav 2020 10 16;10(10):e01799. Epub 2020 Aug 16.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aims: We developed a glaucoma-on-a-chip model to evaluate the viability of retinal ganglion cells (RGCs) against high pressure and the potential effect of neuroprotection.

Methods: A three-layered chip consisting of interconnecting microchannels and culture wells was designed and fabricated from poly-methyl methacrylate sheets. The bottom surface of the wells was modified by air plasma and coated with different membranes to provide a suitable extracellular microenvironment. RGCs were purified from postnatal Wistar rats by magnetic assisted cell sorting up to 70% and characterized by flow cytometry and immunocytochemistry. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36, and 48 hr, with and without adding brain-derived neurotrophic factor (BDNF) or a novel BDNF mimetic (RNYK).

Results: Multiple inlet ports allow culture media and gas into the wells under elevated hydrostatic pressure. PDL/laminin formed the best supporting membrane. RGC survival rates were 85%, 78%, 70%, 67%, and 61% under normal pressure versus 40%, 22%, 18%, 12%, and 10% under high pressure at 6, 12, 24, 36, and 48 hr, respectively. BDNF and RNYK separately reduced RGC death rates about twofold under both normal and elevated pressures.

Conclusion: This model recapitulated the effects of elevated pressure over relatively short time periods and demonstrated the neuroprotective effects of BDNF and RNYK.
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http://dx.doi.org/10.1002/brb3.1799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559618PMC
October 2020

The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study.

Arch Iran Med 2020 07 1;23(7):445-454. Epub 2020 Jul 1.

Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report.

Methods: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations.

Results: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals.

Conclusion: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease.
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http://dx.doi.org/10.34172/aim.2020.41DOI Listing
July 2020

Peripheral blood CD163(+) monocytes and soluble CD163 in dry and neovascular age-related macular degeneration.

FASEB J 2020 06 25;34(6):8001-8011. Epub 2020 Apr 25.

Molecular Biomarkers Nano-Imaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.
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http://dx.doi.org/10.1096/fj.201901902RRDOI Listing
June 2020

Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluation.

Nanomedicine 2020 06 10;26:102181. Epub 2020 Mar 10.

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Dept. of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

As vascular endothelial growth factor in choroidal neovascularization is a major cause of visual loss of the elderlies and diabetics, gene therapy may offer an alternative treatment. However, siRNA instability and inefficient delivery are the main hindrances. To address this issue, we developed a nano-sized siRNA loaded therapeutic delivery system. The chitosan-hyaluronic acid nano-polyplexes were prepared by the modified ionic gelation method. The obtained nano-polyplex with a narrow size distribution, indicated no significant cytotoxicity in the MTT test and proper cellular uptake in confocal images. The RT-PCR analysis indicated remarkable gene silencing on HUVEC cells. The intravitreally administered nano-polyplexes in rabbits overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. Intravitreal injections of the VEGFR-2 siRNA nano-polyplexes significantly reduced the size of the laser-induced choroidal neovascularization, compared to the control group. Consequently, the developed formulation can be a promising candidate for intravitreal delivery of siRNA.
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http://dx.doi.org/10.1016/j.nano.2020.102181DOI Listing
June 2020

Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy.

Arch Iran Med 2019 12 1;22(12):728-730. Epub 2019 Dec 1.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

The TWNK (C10orf2) gene encodes Twinkle, an essential helicase for mtDNA replication. Homozygous mutations in TWNK can lead to mitochondrial DNA depletion syndrome 7 (MTDPS7) that usually manifests as Infantile onset spinocerebellar ataxia (IOSCA). Here, we report a 15-year-old Iranian boy with three main symptoms; ataxia, sensorineural hearing loss and optic nerves atrophy which were accompanied by other symptoms including flexion contracture, dysarthric speech, nystagmus, dystonia and borderline intellectual disability. Whole exome sequencing (WES) revealed a homozygous mutation in his TWNK gene. The mutation was a transversion which replaced a C with A (NM_021830.4 (TWNK):c.874C>A). This nucleotide substitution results in replacing a Threonine with Proline in codon 292 of Twinkle protein (p.Pro292Thr). In silico analyses showed that this amino acid change in Twinkle could be deleterious and disease-causing; therefore, we attribute the symptoms of our patient to this mutation. Our study extended the homozygous mutation spectrum of the TWNK gene that leads to IOSCA.
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December 2019

PRPF31 reduction causes mis-splicing of the phototransduction genes in human organotypic retinal culture.

Eur J Hum Genet 2020 04 25;28(4):491-498. Epub 2019 Oct 25.

Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.

PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splicing in all tissues. However, it is not clear how reduced expression of this general splicing factor leads to retinal restricted disease, retinitis pigmentosa (RP). In this study, we used RNA interference and RNA-sequencing to mimic the PRPF31 haploinsufficiency in human organotypic retinal cultures (HORCs). We examined the effects of PRPF31 deficiency on splicing by analyzing the differential exon usages (DEUs) and intron retentions of the retinal transcriptome. Our results revealed that the PRPF31 deficiency causes mis-splicing of genes involved in RNA processing (PRPF3, PRPF8, PRPF4, and PRPF19) and phototransduction (RHO, ROM1, FSCN2, GNAT2, and GNAT1) in the retina in the PRPF31 reduced samples. Mis-splicing of genes implicated in phototransduction was associated with photoreceptor degeneration observed in RP patients. Our data revealed that PRPF31 deficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on phototransduction and RNA processing.
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http://dx.doi.org/10.1038/s41431-019-0531-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080750PMC
April 2020

mutation as the cause of various clinical manifestations in a family affected with inherited retinal dystrophy.

Ophthalmic Genet 2019 10 16;40(5):436-442. Epub 2019 Oct 16.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

: To reveal the underlying genetic defect in a complex family affected with different clinical features of inherited retinal dystrophy, we carried out whole exome sequencing followed by confirmatory molecular tests.: Complete ophthalmic examinations were performed for available affected family members. Whole exome sequencing, bioinformatics analysis, Sanger sequencing confirmation, and segregation analysis were done to identify the causative mutation.: Clinical findings suggested fundus flavimaculatus as an early clinical feature progressing to an extensive chorioretinal atrophy involving the macula and mid-periphery of the fundus in one parent and central areolar chorioretinal dystrophy (CACD) as the most probable clinical diagnosis in another parent. Macular pattern dystrophy for one of their daughters and a Leber congenital amaurosis (LCA) like phenotype for the daughter with an early onset retinal dystrophy (EORD) phenotype was suggested. We found a known pathogenic nonsense variation in the gene (NM_000322: p.Gln239Ter). The parents with end stage fundus flavimaculatus and CACD diagnosis and their daughter with macular pattern dystrophy were heterozygous for the identified variant. The daughter affected with EORD/LCA like retinal dystrophy was homozygous for the same variation.: In this family, the same pathogenic variant in gene showed a wide range of clinical features of extensive chorioretinal macular atrophy with flecks as fundus falvimaculatus to CACD and macular pattern dystrophy in the heterozygous inheritance pattern and early onset/LCA like retinal dystrophy in the patient who was homozygous for the causative variant.
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http://dx.doi.org/10.1080/13816810.2019.1678178DOI Listing
October 2019

Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran.

Int J Ophthalmol 2019 18;12(8):1330-1336. Epub 2019 Aug 18.

Clinical Research Development Unit of Torfe Medical Center, Shahid Beheshti University of Medical Sciences, Tehran 1149847514, Iran.

Aim: To determine the incidence and risk factors of retinopathy of prematurity (ROP) and the sensitivity of current screening criteria in a tertiary eye center in Tehran, Iran.

Methods: In a cross-sectional observational study, neonates weighing ≤2000 grams at birth or born <34wk gestational age (GA) and all other infants at risk of ROP admitted to the neonatal intensive care unit (NICU) or referred to our ROP clinic were investigated. The incidence of ROP and severe ROP ( patients needing treatment) were determined. The associations between risk factors and the development and severity of ROP were assessed. We also examined the sensitivity of the current national screening guideline in Iran.

Results: Among 207 infants, the incidence of ROP and severe ROP was 33.3% and 11.1%, respectively. Mean GA and birth weight (BW) were significantly lower in ROP non-ROP infants (29±2wk 33±3wk, <0.001; 1274±489 g 1916±550 g, <0.001, respectively). Univariate analysis displayed significant association between ROP incidence and GA, BW, NICU admission period, blood transfusion, surfactant usage, sepsis, intraventricular hemorrhage and patent ductus arteriosus (<0.05 for all). BW [relative risk (RR): 0.857 (0.711-0.873), <0.001], GA [RR: 0.788 (0.711-0.873), <0.001] and blood transfusion [RR: 1.888 (0.995-3.583), =0.052] were independent ROP risk factors. The sensitivity of country-specific screening guidelines was 95.7% and 100% for overall and severe ROP detection, respectively.

Conclusion: ROP incidence is relatively high in Iran. Identifying ROP risk factors results in more accurate screening and reduces the risk of irreversible vision loss. The ROP screening criteria utilized in Iran are efficient at the present time.
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http://dx.doi.org/10.18240/ijo.2019.08.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694057PMC
August 2019

Combination of intravitreal bevacizumab and erythropoietin versus intravitreal bevacizumab alone for refractory diabetic macular edema: a randomized double-blind clinical trial.

Graefes Arch Clin Exp Ophthalmol 2019 Nov 10;257(11):2375-2380. Epub 2019 Aug 10.

Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: To evaluate the effect of three intravitreal bevacizumab (IVB) injections alone or in combination with intravitreal erythropoietin (EPO) in the treatment of refractory diabetic macular edema (DME).

Methods: In a randomized double-blind clinical trial, 48 eyes of 34 diabetic patients with refractory DME were enrolled. Eyes were randomly assigned to receive either 3 monthly injections of 0.05 cc (1.25 mg) IVB plus 0.05 cc (1000 unit) EPO or 0.05 cc (1.25 mg) IVB alone. Main outcome was best-corrected visual acuity (BCVA) changes and secondary outcome was central macular thickness (CMT). The patients were followed for 6 months.

Results: Mean BCVA changes up to 4 and 6 months were insignificant in both groups. It changed from 0.72 ± 0.56 logMAR at baseline to 0.74 ± 0.5 (P = 0.85) and 0.71 ± 0.44 (P = 0.40) in the combination group and from 0.48 ± 0.39 logMAR to 0.47 ± 0.35 (P = 0.48) and 0.52 ± 0.33 (P = 0.69) in the IVB alone group, at 4 and 6 months, respectively. The difference of mean BCVA changes between the groups was insignificant at both 4 and 6 months (P = 0.07 and P = 0.36, respectively). Within the group changes of mean CMT were significant only in the combination group at 4 and 6 months, from 518 ± 134 μ at baseline to 472 ± 151 to 475 ± 167 μ, respectively (P = 0.01 and P = 0.05). Corresponding changes were not significant in the IVB alone group. However, the difference between the groups was not significant at all visits (P = 0.51 and P = 0.71, respectively).

Conclusions: This clinical trial demonstrated that intravitreal erythropoietin had no additional effect to IVB in the treatment of refractory DME in the short term.

Trial Registration: Clinical trials.gov identifier: NCT03821168.
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http://dx.doi.org/10.1007/s00417-019-04383-2DOI Listing
November 2019

Incomplete penetrance of gene for autosomal dominant form of cone-rod dystrophy.

Ophthalmic Genet 2019 06 19;40(3):259-266. Epub 2019 Jun 19.

b Ophthalmic Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

: Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns. : Whole-exome sequencing (WES) was performed for identification of the disease-causing mutations in the probands of both families. The candidate mutations were further confirmed by Sanger sequencing. Samples from five available members of each family were then sequenced for the mutations present in the probands. Comprehensive ocular examinations for all members of the families carrying the mutations were completed by ophthalmologists. : We identified a novel premature stop codon c.310C>T in gene in heterozygote form in two symptomatic and two non-symptomatic members of one family (family-A), and a known mutation c.122G>A in homozygote form in another (family B). c.122G>A has been reported to cause late-onset autosomal dominant form of the disease in previous studies. However, the middle-aged heterozygous carriers of the mutation in this family showed normal phenotype. : The gene has been previously linked to the autosomal dominant form of cone-rod dystrophy. We report incomplete penetrance of gene for autosomal dominant form of the disease. Incomplete penetrance of the mutations may be partly caused by the influence of other genes in the complex genetic network underlying retinal regulation.
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http://dx.doi.org/10.1080/13816810.2019.1622023DOI Listing
June 2019

Generation of Retinal Pigmented Epithelium-Like Cells from Pigmented Spheres Differentiated from Bone Marrow Stromal Cell-Derived Neurospheres.

Tissue Eng Regen Med 2019 06 3;16(3):253-263. Epub 2019 May 3.

Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Rashid Yasemi Street, Upper than Mirdamad St. Vali- Asr. St., 1996816747 Tehran, Iran.

Background: Retinal degeneration causes blindness, and cell replacement is a potential therapy. The purpose of this study is to formation of pigmented neurospheres in a simple medium, low-cost, high-performance manner over a short period of time while expressing markers of RPE cells and the activation of specific genes of the pigment cells. Also, these neurospheres have the ability to produce a monolayer of retinal pigment epithelium-like cells (RPELC) with the ability of photoreceptor outer segment phagocytosis.

Methods: BMSC were isolated from pigmented hooded male rats and were immunoreactive to BMSC markers, then converted into neurospheres, differentiated into pigmented spheres (PS), and characterized using Retinal pigment epithelium-specific 65 kDa protein (RPE65), Retinaldehyde-binding protein 1 (CRALBP) and orthodenticle homeobox 2 (OTX2) markers by immunocytochemistry, RT-PCR and RT-qPCR. The PS were harvested into RPELC. The functionality of RPELC was evaluated by phagocytosis of fluorescein-labeled photoreceptor outer segment.

Results: The BMSC immunophenotype was confirmed by immunostained for fibronectin, CD90, CD166 and CD44. These cells differentiated into osteogenic and lipogenic cells. The generated neurospheres were immunoreactive to nestin and stemness genes. The PS after 7-14 days were positive for RPE65 (92.76-100%), CRALBP (95.21-100%) and OTX2 (94.88-100%), and after 30 days RT-PCR, qPCR revealed increasing in gene expression. The PS formed a single layer of RPELC after cultivation and phagocyte photoreceptor outer segments.

Conclusion: Bone marrow stromal stem cells can differentiate into functional retinal pigmented epithelium cells in a simple, low-cost, high-performance manner over a short period of time. These cells due to expressing the RPELC genes and markers can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration as well as retinitis pigmentosa.
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http://dx.doi.org/10.1007/s13770-019-00183-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542896PMC
June 2019

Effects of intravitreal connective tissue growth factor neutralizing antibody on choroidal neovascular membrane-associated subretinal fibrosis.

Exp Eye Res 2019 07 25;184:286-295. Epub 2019 Apr 25.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Connective tissue growth factor (CTGF) plays an essential role in the regulation of extracellular matrix proteins and pro-fibrotic and angiogenic factors. This experimental research was conducted to evaluate if CTGF is elevated after induction of a choroidal neovascular membrane (CNVM) and whether intravitreal anti-CTGF without and with intravitreal bevacizumab (IVB) may have any effect on the CNVM associated sub-retinal fibrosis. In adherence to ARRIVE guidelines, CNVM was induced by laser spots in the right eye retinas of ninety-four pigmented rats. Quantitative real-time reverse transcription PCR (qRT-PCR) and western-blot analysis were performed on sclerochoroidal tissues of forty-four rats before and at different time intervals after laser application. The remaining fifty rats were randomly divided into five groups after laser application. Group A received intravitreal injection of 2  μl of the 50 μg/ml anti-CTGF. In group B, intravitreal injection of 2  μl of 25 mg/ml bevacizumab was performed. Group C received 1  μl intravitreal anti-CTGF and 1  μl IVB. Group D did not receive any intravitreal injection as the control group. In group E, intravitreal injection of 2  μl of nonspecific purified mouse IgG antibody was performed as the placebo group. After two weeks, double immunohistochemistry was performed by isolectin B4 and anti-collagen type1 on the sclerochoroidal flat-mounts. Masked measurement of the fluorescent images of the CNVM and CNVM associated sub-retinal fibrosis areas was performed using the image J software. Ctgf mRNA and CTGF protein levels increased to the maximum level in 24 h after laser application and remained higher than the control level up to the 14th day for the Ctgf mRNA and up to the 7th day for the CTGF protein level. Means of CNVM associated sub-retinal fibrosis areas in three treatment groups (A, B and C) were significantly less than the control (D) and placebo (E) groups (P < 0.001, <0.05, <0.001 respectively). For groups A and C, mean CNVM associated sub-retinal fibrosis areas were also significantly less than group B (P < 0.05 and < 0.01, respectively). In conclusion, this study showed significant reduction of the CNVM associated sub-retinal fibrosis via inhibition of the CTGF which mediates the final steps of fibrosis in various inflammatory and angiogenic pathways.
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http://dx.doi.org/10.1016/j.exer.2019.04.027DOI Listing
July 2019

Modeling a Telemedicine Screening Program for Diabetic Retinopathy in Iran and Implementing a Pilot Project in Tehran Suburb.

J Ophthalmol 2019 4;2019:2073679. Epub 2019 Mar 4.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: To model a community-based telescreening program for diabetic retinopathy (DR) in Iran and to implement a pilot project at the Iranian Diabetes Society (IDS) branch in a Tehran suburb.

Methods: In this mixed model study, a web application called the "Iranian Retinopathy Teleophthalmology Screening (IRTOS)" was launched. The educational course for DR screening was established for general practitioners (GPs). Registered patients in IDS branch were recalled for fundus photography; images were transferred to the reading center via IRTOS to be graded by GPs, and patients were informed about the results via mobile messaging. All images were independently reviewed by a retina specialist as the gold standard. Patients who required further assessment were referred to an eye hospital.

Results: Overall, 604 subjects with diabetes were screened; of these, 50% required referral. The sensitivity and specificity for diagnosis of any stage of DR by trained GPs were 82.8% and 86.2%, respectively, in comparison to the gold standard. The corresponding values for detecting any stage of diabetic macular edema (DME) were 63.5% and 96.6%, respectively.

Conclusions: Telescreening was an effective method for detecting DR in a Tehran suburb. This screening model demonstrated its capacity for promoting diabetic eye care services at the national level. However, the sensitivity for detecting DME needs to be improved by modifying the referral pathway and promoting the skill of GPs.
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http://dx.doi.org/10.1155/2019/2073679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425400PMC
March 2019

In Vivo Evaluation of PAX6 Overexpression and NMDA Cytotoxicity to Stimulate Proliferation in the Mouse Retina.

Sci Rep 2018 12 7;8(1):17700. Epub 2018 Dec 7.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Retinal degenerative diseases, due to the lack of regeneration systems and self-renewable cells, often lead to visual impairment. Pax6 is a pleiotropic transcription factor and its expression level determines self-renewal status or differentiation of retinal cells. Here, we investigated the fate of simultaneous induction of retinal ganglion cell death and Pax6 overexpression in retro-differentiation of retinal cells and their commitment to re-enter into the cell cycle. Induction of acute retinal ganglion cell death and generation of mouse experimental model was performed by N-methyl D-aspartic acid (NMDA) injection. Recombinant AAV2 virus harboring PAX6 cDNA and reporter gene was injected into untreated and model mouse eyes. Histological analyses, including IHC and retinal flatmounts immunostaining were performed. The number of Ki67+ cells was clearly increased in model mice, presumably due to NMDA treatment and regardless of Pax6 over-expression. Unlike previous studies, Ki67+ cells were found in GCL layer and interestingly ONL cells expressed Sox2 stemness marker after NMDA cytotoxicity. The potential of retinal cells for robust Ki67 expression, after injury, and expression of Sox2, confirmed their intrinsic plasticity and made a vivid prospect for retinal regenerative medicine.
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http://dx.doi.org/10.1038/s41598-018-35884-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286369PMC
December 2018

Peptide selected by phage display increases survival of SH-SY5Y neurons comparable to brain-derived neurotrophic factor.

J Cell Biochem 2018 Nov 1. Epub 2018 Nov 1.

Department of Electronics, School of Electrical and Computer Engineering, Tehran University, Tehran, Iran.

Brain-derived neurotrophic factor (BDNF) is a well-known neuroprotectant and a potent therapeutic candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we designed and developed BDNF-mimicking small peptides as an alternative to circumvent these problems. A phage-displayed peptide library was screened using BDNF receptor (neurotrophic tyrosine kinase receptor type2 [NTRK2]) and evaluated by ELISA. The peptide sequences showed similarity to loop2 of BDNF, they were recognized as discontinuous epitopes though. Interestingly, in silico molecular docking showed strong interactions between the peptide three-dimensional models and the surface residues of the NTRK2 protein at the IgC2 domain. A consensus peptide sequence was then synthesized to generate a mimetic construct (named as RNYK). The affinity binding and function of this construct was confirmed by testing against the native structure of NTRK2 in SH-SY5Y cells in vitro using flow-cytometry and MTT assays, respectively. RNYK at 5 ng/mL prevented neuronal degeneration of all- trans-retinoic acid-treated SH-SY5Y with equal efficacy to or even better than BDNF at 50 ng/mL.
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http://dx.doi.org/10.1002/jcb.28036DOI Listing
November 2018

Effects of fibrin glue as a three-dimensional scaffold in cultivated adult human retinal pigment epithelial cells.

J Biomater Appl 2018 10 13;33(4):514-526. Epub 2018 Sep 13.

4 Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study was conducted to examine morphological, genotypic, and phenotypic alterations occurring in cultured adult human retinal pigment epithelial cells when encapsulated with different concentrations of fibrin glue. Cultivated adult human retinal pigment epithelial cells were encapsulated with different concentrations of fibrin glue, namely FG1 (42 mg/dl), FG2 (84 mg/dl), FG3 (124 mg/dl), FG4 (210 mg/dl), followed by the evaluation of genetic and cytomorphological changes and protein expression. Cultured adult human retinal pigment epithelial cells showed dendritiform morphology during the early days of encapsulation with fibrin glue. Moreover, an increasing inhibitory effect on cell growth was observed with increasing concentrations of fibrin glue. At the transcriptional level, the expression of MMP2, PAX6, and ITGB1 in FG1-encapsulated cells was significantly higher than that in other treated groups; however, the expression of ACTA2 was lower in all fibrin glue-encapsulated groups compared to that in the controls. Immunocytochemistry showed that FG2-encapsulated cells expressed cytokeratin 8/18, RPE65, and ZO-1 proteins, but not PAX6. In conclusion, fibrin glue at a concentration of 84 mg/dl allows proper encapsulation of adult human retinal pigment epithelial cells, while preserving the morphometric, genotypic, and phenotypic features of the cells. This three-dimensional biopolymer can be considered a reliable vehicle for retinal pigment epithelium cell transplantation in cell-based therapies.
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http://dx.doi.org/10.1177/0885328218799506DOI Listing
October 2018

COL18A1 is a candidate eye iridocorneal angle-closure gene in humans.

Hum Mol Genet 2018 11;27(21):3772-3786

School of Biology, University College of Science, University of Tehran, Tehran, Iran.

Primary angle-closure glaucoma (PACG) is a common form of glaucoma in the Far East. Its defining feature is iridocorneal angle closure. In addition to PACG, indications of angle closure are included in the diagnostic criteria of related conditions primary angle-closure suspect (PACS) and primary angle closure (PAC). To the best of our knowledge, a causative gene for iridocorneal angle closure in humans has not been identified. This study aimed to identify the genetic cause of iridocorneal angle closure in a pedigree with at least 10 individuals diagnosed with PACS, PAC or PACG. Results of linkage analysis, segregation analysis of 44 novel variations, whole exome sequencing of 10 individuals, screenings of controls and bioinformatics predictions identified a mutation in COL18A1 that encodes collagen type XVIII as the most likely cause of angle closure in the pedigree. The role of COL18A1 in the etiology of Knobloch syndrome (KS) that is consistently accompanied by optic anomalies, available functional data on the encoded protein and the recognized role of collagens and the extracellular matrix in glaucoma pathogenesis supported the proposed role of the COL18A1 mutation in the pedigree. Subsequent identification of other COL18A1 mutations in PACS affected individuals of two unrelated families further supported that COL18A1 may affect angle closure. These PACS individuals were parents and grandparents of KS-affected children. In conclusion, a gene that affects angle closure in humans, a critical feature of PACG, has been identified. The findings also reinforce the importance of collagens in eye features and functions.
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http://dx.doi.org/10.1093/hmg/ddy256DOI Listing
November 2018

Novel Mutations in Gene in Families with Gelatinous Drop-like Corneal Dystrophy (GDLD).

Int J Mol Cell Med 2017 11;6(4):204-211. Epub 2017 Dec 11.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In the current study, we conducted a mutation screening of tumor-associated calcium signal transducer 2 () gene in six consanguineous Iranian families with gelatinous drop-like corneal dystrophy (GDLD), in order to find the causative mutations. Detailed eye examination was performed by ophthalmologist to confirm GDLD in patients. To detect the possible mutations, direct Sanger sequencing was performed for the only exon of gene, and its boundary regions in all patients. In the patients with GDLD, the corneal surface showed lesions with different shapes from mild to severe forms depending on the progress of the disease. The patients showed grayish corneal deposits as a typical mulberry form, corneal dystrophy along with corneal lipid deposition, and vascularization. Targeted Sanger sequencing in gene revealed the causative mutations in this gene in all studied families. Our study expanded the mutational spectrum of which along with the related symptoms could help with the diagnosis, and management of the disease.
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http://dx.doi.org/10.22088/BUMS.6.4.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004293PMC
December 2017

Human organotypic retinal flat-mount culture (HORFC) as a model for retinitis pigmentosa11.

J Cell Biochem 2018 08 10;119(8):6775-6783. Epub 2018 May 10.

Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.

The splicing factor PRPF31 is the most commonly mutated general splicing factor in the retinitis pigmentosa. We used a rapid, convenient and cost effective transfection method with an efficient PRPF31 knockdown in HORFC in order to study the effect of PRPF31 downregulation on retinal gene expressions in an ex vivo model. Modified calcium phosphate method was used to transfect HORFC by PRPF31 siRNA. Different times and doses of siRNA for transfection were assayed and optimum condition was obtained. PRPF31 mRNA and protein downregulation were assessed by qRTPCR and Western blot. The tissue viability of HORFC was measured using the MTT. ImageJ analysis on stained retinal sections by immunohistochemistry was used for thickness measurement of outer nuclear photoreceptor layer. The PRPF31 gene downregulation effects on retinal specific gene expression were analyzed by qRTPCR. A total of 50 nM of PRPF31 siRNA transfection after 63 h in HORFC, showed the optimum reduction in the level of PRPF31 mRNA and protein as shown by qRTPCR and Western blot (over 90% and 50% respectively). The PRPF31 mRNA silencing with calcium phosphate had no effect on cell viability in the period of the experiment. Thickness measurement of outer nuclear photoreceptor layer with IHC showed the significant reduction after 63 h of study (P value = 0.02). siRNA induced PRPF31 knockdown, led to reduction of retinal specific mRNA gene expression involved in phototransduction (RHO, GNAT1, RP1), photoreceptor structure (ROM1, FSCN2, CA4, SEMA4) and transcription factor (CRX) (fold change >5), after 63 h.
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http://dx.doi.org/10.1002/jcb.26871DOI Listing
August 2018

Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline.

J Ophthalmic Vis Res 2018 Apr-Jun;13(2):158-169

Standardization and CPG Development Office, Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran.

Purpose: To provide the clinical recommendations for the administration of intravitreal anti-vascular endothelial growth factor (VEGF) drugs especially bavacizumab for ocular vascular diseases including diabetic macular edema, neovascular age-related macular degeneration, myopic choroidal neovascularization, retinal vein occlusion and central serous chorioretinopathy.

Methods: Twenty clinical questions were developed by the guideline technical committee. Relevant websites and databases were searched to find out the pertinent clinical practice guidelines to answer the questions. The technical committee provided possible answers (scenarios) according to the available evidences for each question. All scenarios along with their levels of evidence and the supported articles were sent to the experts for external review. If the experts did not agree on any of the scenarios for one particular clinical question, the technical committee reviewed all scenarios and their pertinent evidences and made the necessary decision. After that, the experts were asked to score them again. All confirmed scenarios were gathered as the final recommendations.

Results: All the experts agreed on at least one of the scenarios. The technical committee extracted the agreed scenario for each clinical question as the final recommendation. Finally, 56 recommendations were developed for the procedure of intravitreal anti-VEGF injection and their applications in the management of ocular vascular diseases.

Conclusion: The implementation of this guideline can standardize the management of the common ocular vascular diseases by intravitreal injection of anti-VEGF agents. It can lead to better policy-making and evidence-based clinical decision by ophthalmologists and optimal evidence based eye care for patients.
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http://dx.doi.org/10.4103/jovr.jovr_50_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905310PMC
May 2018

Survival and Migration of Adipose-Derived Stem Cells Transplanted in the Injured Retina.

Exp Clin Transplant 2018 Apr 12;16(2):204-211. Epub 2017 Oct 12.

From the Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: Transplantation of stem cells is one of the approaches to treat retinal diseases. Our objective was to determine whether adipose-derived stem cell transplant can survive and migrate in the injured retina using a sodium iodate model for the pigmented retinal epithelium injury.

Materials And Methods: The adipose-derived stem cells were isolated from male albino Sprague-Dawley rats and labeled with DiI so as to track the transplants in the subretinal space. Retinal pigmented epithelium damage was induced by retro-orbital sinus sodium iodate injection (40 mg/kg) into albino Sprague-Dawley rats. Four weeks after transplantation, the eyeballs were fixed in 4% paraformaldehyde and cut with cryostat. The eyeballs were serially sectioned along the vertical meridian. Cryosections were from the full length of the retina and passing through the optic nerve head. The survival and migration of transplanted cells were assessed.

Results: Sodium iodate selectively destroyed the retinal pigmented epithelium layer. The transplanted cells incorporated into the retinal pigmented epithelium layer, perhaps differentiating into a retinal pigmented epithelium phenotype. The transplanted cells were located in the subretinal space; after 4 weeks, some were observed in the retinal pigmented epithelium layer.

Conclusions: We found that adipose-derived stem cells survived for 4 weeks after transplantation and migrated into the retinal pigmented epithelium layer.
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http://dx.doi.org/10.6002/ect.2016.0235DOI Listing
April 2018

A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease.

Clin Exp Optom 2018 03 18;101(2):255-259. Epub 2017 Sep 18.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Norrie disease (ND) is a rare, X-linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND.

Methods: Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients.

Results: A GG dinucleotide insertion in exon 3 (c.240_241insGG) of NDP was detected in all patients. The mutation caused a frameshift and an early stop codon (p.Phe81Glyfs*23).

Conclusions: A novel mutation was found in the NDP gene in the affected males of the family. As the mutation was absent in the normal male members of the family, it should be the genetic cause of the disease.
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http://dx.doi.org/10.1111/cxo.12599DOI Listing
March 2018

Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

Arch Iran Med 2017 Aug;20(8):525-537

National institute Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.
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August 2017
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