Publications by authors named "Bingqian Liu"

110 Publications

Outcomes of macular buckling surgery in myopic foveal detachment eyes with and without disrupted ellipsoid zone band: a case-control study.

Graefes Arch Clin Exp Ophthalmol 2021 Mar 6. Epub 2021 Mar 6.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.

Purpose: To compare the outcomes of macular buckling (MB) surgery between myopic foveal detachment (FD) eyes with and without ellipsoid zone (EZ) disruption.

Methods: A retrospective, case-control study. Forty-four consecutive eyes from 44 patients received MB surgery for myopic FD between November 2017 and January 2019 were included. The eyes were divided into two groups according to the integrity of EZ on spectral-domain optical coherence tomography (SD-OCT): 28 eyes with disrupted EZ band and 16 eyes with intact EZ band. Main outcome measures were visual acuity and the duration of subfoveal fluid (SFF) after MB.

Results: The mean follow-up time was 17.64 ± 6.61 and 16.06 ± 5.78 months in the disrupted EZ and intact EZ group, respectively (P = 0.430). The logMAR best-corrected visual acuity (BCVA) improved significantly, from 1.13 ± 0.46 and 1.12 ± 0.39 at baseline to 0.85 ± 0.65 (P = 0.002) and 0.53 ± 0.33 (P = 0.000) for the disrupted EZ group and intact EZ group, respectively. The mean visual improvement was 15.00 ± 14.14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for the disrupted EZ group and 26.88 ± 19.48 ETDRS letters for the intact EZ group. Significant difference was found on both final postoperative BCVA (P = 0.035) and visual improvement (P = 0.025). At 6 months, SFF remained in 53.57% (15/28) of the eyes in the disrupted EZ group and in only 12.50% (2/16) of the eyes in the intact EZ group (P = 0.018).

Conclusion: The intact EZ group showed better functional and anatomical outcomes than the disrupted EZ group after MB surgery.
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http://dx.doi.org/10.1007/s00417-021-05123-1DOI Listing
March 2021

Microinvasive pars plana vitrectomy versus panretinal photocoagulation in the treatment of severe non-proliferative diabetic retinopathy (the VIP study): study protocol for a randomised controlled trial.

BMJ Open 2021 02 22;11(2):e043371. Epub 2021 Feb 22.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

Introduction: Diabetic retinopathy (DR) is the main cause of adult visual impairment worldwide. Severe non-proliferative DR (sNPDR) is an important clinical intervention stage. Currently, panretinal photocoagulation (PRP) is the standard treatment for sNPDR. However, PRP alone cannot completely prevent NPDR progression. One explanation might be that PRP does not remove the detrimental vitreous that plays an important role in DR progression. Microinvasive pars plana vitrectomy (PPV) was shown to be a safe and effective method to treat late-stage proliferative DR (PDR) by completely removing the pathological vitreous. However, whether PPV is effective in controlling sNPDR remains unknown. In this trial, we aim to compare the effectiveness of microinvasive PPV with that of PRP for sNPDR progression control.

Methods And Analysis: This single centre, parallel group, randomised controlled trial aims to evaluate the clinical efficacy of microinvasive PPV in preventing the progression of sNPDR compared with PRP. A total of 272 adults diagnosed with sNPDR will be randomised 1:1 to the microinvasive PPV and PRP groups. The primary outcome is the disease progression rate, calculated as the rate of sNPDR progressed to PDR from baseline to 12 months after treatment. The secondary outcomes include the change in best-corrected visual acuity, re-treatment rate, diabetic macular oedema occurrence, change in central retinal thickness, change in the visual field, cataract occurrence and change in the quality of life.

Ethics And Dissemination: The Ethics Committee of Zhongshan Ophthalmic Center approved this study (2019KYPJ108). The results will be presented at scientific meetings and submitted for publication to peer-reviewed journals.

Trial Registration Number: NCT04103671.
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http://dx.doi.org/10.1136/bmjopen-2020-043371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903093PMC
February 2021

Changes in the Choroidal Thickness after Macular Buckling in Highly Myopic Eyes.

Retina 2021 Jan 21. Epub 2021 Jan 21.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Purpose: To assess changes in the choroidal thickness after macular buckling in eyes with high myopia.

Methods: Highly myopic eyes that underwent macular buckling surgery were retrospectively analyzed. Data of swept source-optical coherence tomography scanning at baseline and at 1, 3, 6, 12, and 18 months after macular buckling were collected. Subfoveal choroidal thickness (SFCT) and choroidal thickness at 750 μm superior, inferior, nasal, and temporal to the fovea were measured. The total choroidal area, vascular area and stromal area were measured by the binarization method. The choroidal vascularity index (CVI) was calculated by dividing the vascular area by the total choroidal area.

Results: Forty-one eyes were included in the final analysis. The SFCT increased from 49.85±31.23 µm preoperatively to 75.74±37.89 µm 1 month after macular buckling (P < 0.001), then decreased over time, coinciding with the trends of parafoveal choroidal thickness, total choroidal area, vascular area, and stromal area. The SFCT was restored to the preoperative level six months postoperatively (P=0.202) and remained stable until the end of follow-up. The CVI increased at 1 and 3 months postoperatively (P = 0.001 and 0.005, respectively).

Conclusions: The choroid thickened in the early postoperative period. The compression force of the buckle implant might disturb microcirculatory drainage and contribute to the thickening. The choroid spontaneously recovered to the preoperative level over time.
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http://dx.doi.org/10.1097/IAE.0000000000003125DOI Listing
January 2021

TXNIP positively regulates the autophagy and apoptosis in the rat müller cell of diabetic retinopathy.

Life Sci 2021 Feb 4;267:118988. Epub 2021 Jan 4.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. Electronic address:

Aims: Diabetic retinopathy (DR) can cause vision loss in patients with diabetes. The present study evaluated the expression of thioredoxin interacting protein (TXNIP) and investigated the role of TXNIP in autophagy and apoptosis of DR.

Main Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to measure the expression level of the targets. Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/cas9) method was applied for knockout of TXNIP. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay and flow cytometry were utilized to detect the apoptosis. Cell Counting Kit-8 (CCK-8) assay was used to evaluate the cell viability. EdU assay was carried out to measure the cell proliferation ability. Retinal immunohistochemistry, retinal frozen section immunofluorescence as well as the electroretinogram (ERG) recording were implemented to detect the function of the retina.

Key Findings: TXNIP was up-regulated under hyperglycemic condition both in vivo and in vitro. Overexpression of TXNIP activated the autophagy and apoptosis in the rat müller cell. Knockout of TXNIP reduced the autophagy and apoptosis in the rat müller cell under high glucose condition. TXNIP positively regulates autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway. Knockdown of TXNIP improved the visual response to light stimulus of DR.

Significance: Our study unraveled for the first time that TXNIP positively regulates the autophagy in rat müller cell under high glucose condition by inhibiting the PI3K/AKT/mTOR signaling pathway, providing a novel understanding in the pathogenesis of DR and suggesting a potential new therapeutic target of DR.
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http://dx.doi.org/10.1016/j.lfs.2020.118988DOI Listing
February 2021

Macular buckling versus vitrectomy on macular hole associated macular detachment in eyes with high myopia: a randomised trial.

Br J Ophthalmol 2021 Jan 4. Epub 2021 Jan 4.

Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, Guangdong, China

Aim: To compare the efficacy of macular buckling (MB) and pars plana vitrectomy (PPV) for full-thickness macular holes (FTMH) and associated macular detachment (MD) in highly myopic eyes.

Methods: Prospective interventional case series of eyes undergoing PPV or MB for FTMH and MD.

Main Outcome Measures: Best-corrected visual acuity (BCVA) at postoperative month 24. Other measured outcomes include the initial surgical success rate, macular hole closure rate and the progression of myopic maculopathy.

Results: A total of 53 eyes from 53 participants were included in this study (26 participants receiving MB and 27 participants receiving PPV), and finally 49 eyes from 49 participants (25 participants in the MB group and 24 participants in the PPV group) were analysed. At postoperative month 24, the BCVA had improved significantly in those that underwent either MB (p<0.001) or PPV (p=0.04). The difference between the groups was not significant (p=0.653). The surgical failure rate after the primary treatment was significantly higher in the PPV group than the MB group (25.00% vs 4.00%, respectively; p=0.04). The macular closure rate was higher in the MB group compared with the PPV group, but the difference was not statistically significant (64.00% vs 58.33%, respectively; p=0.45). Myopic maculopathy development may be more severe following PPV than following MB surgery.

Conclusion: Patients with high myopia obtained anatomical and functional improvements from either MB or PPV. However, MB achieved a significantly higher success rate in retinal reattachment compared with PPV.

Trial Registration Number: NCT03433547.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317800DOI Listing
January 2021

Development and validation of a deep learning system to screen vision-threatening conditions in high myopia using optical coherence tomography images.

Br J Ophthalmol 2020 12 21. Epub 2020 Dec 21.

Centre of Precision Medicine, Sun Yat-sen University, Guangzhou, China.

Background/aims: To apply deep learning technology to develop an artificial intelligence (AI) system that can identify vision-threatening conditions in high myopia patients based on optical coherence tomography (OCT) macular images.

Methods: In this cross-sectional, prospective study, a total of 5505 qualified OCT macular images obtained from 1048 high myopia patients admitted to Zhongshan Ophthalmic Centre (ZOC) from 2012 to 2017 were selected for the development of the AI system. The independent test dataset included 412 images obtained from 91 high myopia patients recruited at ZOC from January 2019 to May 2019. We adopted the InceptionResnetV2 architecture to train four independent convolutional neural network (CNN) models to identify the following four vision-threatening conditions in high myopia: retinoschisis, macular hole, retinal detachment and pathological myopic choroidal neovascularisation. Focal Loss was used to address class imbalance, and optimal operating thresholds were determined according to the Youden Index.

Results: In the independent test dataset, the areas under the receiver operating characteristic curves were high for all conditions (0.961 to 0.999). Our AI system achieved sensitivities equal to or even better than those of retina specialists as well as high specificities (greater than 90%). Moreover, our AI system provided a transparent and interpretable diagnosis with heatmaps.

Conclusions: We used OCT macular images for the development of CNN models to identify vision-threatening conditions in high myopia patients. Our models achieved reliable sensitivities and high specificities, comparable to those of retina specialists and may be applied for large-scale high myopia screening and patient follow-up.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317825DOI Listing
December 2020

Patterns of Fundus Autofluorescence in Eyes with Myopic Atrophy Maculopathy: A Consecutive Case Series Study.

Curr Eye Res 2020 Dec 17:1-5. Epub 2020 Dec 17.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

: To investigate the patterns of fundus autofluorescence (FAF) in patients with different grades of myopic atrophy maculopathy (MAM).: Patients with MAM who visited Zhongshan Ophthalmic Center from January 2018 to December 2019 were screened. All patients received comprehensive ophthalmologic examinations as well as FAF imaging. The atrophic severity of each eye was identified based on the META-PM classification system, including no myopic retinal lesions (C0), tessellated fundus only (C1), diffuse chorioretinal atrophy (C2), patchy chorioretinal atrophy (C3), and macular atrophy (C4).: Eighty-nine consecutive patients with 137 affected eyes were included. Four different autofluorescence (AF) patterns were detected: unremarkable AF (48 eyes in C1 and 18 eyes in C2, 48.2%), compound AF (2 eyes in C1 and 12 eyes in C2, 10.2%), patchy AF defect (5 eyes in C2 and 34 eyes in C3, 28.5%), and macular AF defect (18 eyes in C4, 13.1%). Moreover, AF patterns were significantly correlated with age (r = 0.419, < .001), best-corrected visual acuity (BCVA) (r = 0.592, < .001), axial length (AL) (r = 0.529, < .001), and subfovial choroidal thickness (SFCT) (r = -0.728, < .001). In addition, with the help of FAF, 14.3% (5/35) of eyes initially categorized as C2 merely based on color fundus photographs (CFP) should be categorized as C3.: The severity of FAF in eyes with MAM was significantly correlated with myopic characteristics. FAF might be beneficial for detecting unremarkable patchy chorioretinal atrophy on CFP of MAM.
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http://dx.doi.org/10.1080/02713683.2020.1857780DOI Listing
December 2020

CLINICAL CHARACTERISTICS OF EYES WITH DIFFERENT GRADES OF MYOPIC TRACTION MACULOPATHY - BASED ON THE ATN CLASSIFICATION SYSTEM.

Retina 2020 Nov 20. Epub 2020 Nov 20.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.

Purpose: To analyze clinical characteristics in eyes with myopic traction maculopathy (MTM).

Methods: 991 patients (1334 eyes) with MTM, who visited Zhongshan Ophthalmic Center from January 2014 to December 2019, were involved. MTM was classified into six grades according to the ATN classification system: no macular schisis (T0); inner or outer foveoschisis (FS) (T1); inner and outer FS (T2); foveal detachment (FD) (T3); full-thickness macular hole (FTMH) (T4); and macular hole retinal detachment (MHRD) (T5).

Results: 778 (58.32%) eyes were in T0, 157 (11.77%) in T1, 177 (13.27%) in T2, 129 (9.67%) in T3, 45 (3.37%) in T4, and 48 (3.67%) in T5. With the severity of MTM, age increased and best-corrected visual acuity (BCVA) became worse (P<0.001). However, no significant differences were found on spherical equivalent refraction (SER) or axial length (AL) among different grades of MTM (P>0.05). Moreover, significant differences on BCVA, SER, AL and staphyloma rate existed between eyes with inner FS and eyes with outer FS (P<0.01), but not between eyes with outer FS and eyes with both inner FS and outer FS (P>0.05). Besides, significant differences were found on SER, AL and staphyloma rate between FTMH with and without macular schisis (P<0.001).

Conclusion: SER and AL were not correlated with the severity of MTM in this cohort. It might be preferable to categorize eyes with outer FS and eyes with both inner FS and outer FS as a same grade. Potential difference in the pathogenesis between FTMH with and without macular schisis might exist.
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http://dx.doi.org/10.1097/IAE.0000000000003043DOI Listing
November 2020

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer.

Front Mol Biosci 2020 31;7:218. Epub 2020 Aug 31.

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa.

Methods: Bioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed.

Results: Bioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis.

Conclusion: RAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa.
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http://dx.doi.org/10.3389/fmolb.2020.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488983PMC
August 2020

DEEP PHENOTYPING AND FURTHER INSIGHTS INTO ITM2B-RELATED RETINAL DYSTROPHY.

Retina 2021 Apr;41(4):872-881

Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.

Purpose: To reappraise the presentation and the course of ITM2B-related retinal dystrophy and give further insights into ITM2B expression in the retina.

Methods: The clinical data of nine subjects with ITM2B-related retinal dystrophy were retrospectively reviewed. The genetic mutation was assessed for its influence on splicing in cultured fibroblasts. The cellular expression of ITM2B within the inner retina was investigated in wild-type mice through mRNA in situ hybridization.

Results: All patients complained of decreased vision and mild photophobia around their twenties-thirties. The peculiar feature was the hyperreflective material on optical coherence tomography within the inner retina and the central outer nuclear layer with thinning of the retinal nerve fiber layer. Although retinal imaging revealed very mild or no changes over the years, the visual acuity slowly decreased with about one Early Treatment Diabetic Retinopathy Study letter per year. Finally, full-field electroretinography showed a mildly progressive inner retinal and cone dysfunction. ITM2B mRNA is expressed in all cellular types of the inner retina. Disease mechanism most likely involves mutant protein misfolding and/or modified protein interaction rather than misplicing.

Conclusion: ITM2B-related retinal dystrophy is a peculiar, rare, slowly progressive retinal degeneration. Functional examinations (full-field electroretinography and visual acuity) seem more accurate in monitoring the progression in these patients because imaging tends to be stable over the years.
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http://dx.doi.org/10.1097/IAE.0000000000002953DOI Listing
April 2021

Anti-glaucoma potential of hesperidin in experimental glaucoma induced rats.

AMB Express 2020 May 18;10(1):94. Epub 2020 May 18.

Department of Ophthalmology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Xuzhou Medical University Affiliated Hospital of Lianyungang, The First People's Hospital of Lianyungang, No. 6 Zhenhua East Road, Haizhou District, Lianyungang, 222002, China.

Glaucoma is well-known clinical eye conditions that damage the optic nerve due to abnormal pressure conditions in eye. Hesperidin is well-known glycoside widely present in the citrus fruits, and its aglycone form is known as hesperetin. Hesperidin is major flavone found in orange fruits. Hypotensive effect of hesperidin in acute and chronic glaucoma rats, glutamate level in vitreous humour and glutathione (GSH) level in aqueous humour were determined following 25, 50 and 100 mg/kg of hesperidin treatment. Acetazolamide (5 mg/kg) was used as positive control. Hesperidin treatment significantly reduced the increased intraocular pressure (IOP) level in dextrose induced ocular hypertension than saline treated rats. The effect of hesperidin was comparable to the positive control acetazolamide. Similarly, hesperidin treatment significantly reduced the IOP level in prednisolone acetate induced ocular hypertension than saline treated rats. In the aqueous humour, hesperidin treatment increased the glutathione level 125%, 184.4% and 231.2% at 25, 50 and 100 mg/kg of hesperidin respectively. In the vitreous humour, hesperidin treatment reduced the glutamate level 9.9%, 13.2% and 25.3% at 25, 50 and 100 mg/kg of hesperidin respectively. Histopathological analysis of normal saline treated rats showed morphological alteration in ciliary bodies. However, rats treated with hesperidin showed the reduced level of morphological alteration in ciliary bodies. Taking all these data together, it is suggested that the hesperidin supplementation was effective against glaucoma in experimental rats.
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http://dx.doi.org/10.1186/s13568-020-01027-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235152PMC
May 2020

Patterns of Choroidal Deepening in Highly Myopic Eyes with Dome-Shaped Macula.

Curr Eye Res 2020 08 27;45(8):1017-1023. Epub 2019 Dec 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou, China.

Purpose: To investigate the patterns and characteristics of choroidal deepening (CD) in highly myopic eyes with a dome-shaped macula (DSM).

Methods: A retrospective analysis of vertical and horizontal optical coherence tomography (OCT) scans across the central fovea was conducted. An inward bulge greater than 50μm at either the vertical or horizontal OCT images of the macula was defined as DSM and was analyzed.

Results: Among the 155 eyes, a vertical oval-shaped DSM was present in eight eyes (5.16%), a horizontal oval-shaped in 102 eyes (65.81%), and a round DSM in 45 eyes (29.03%). Vertical oval-shaped DSM exhibited the longest axial length (AL) and the largest dome base among the three types ( < .05). The CD in DSM was classified into three distinct patterns: sub-dome choroidal deepening (SDCD), peri-dome choroidal deepening (PDCD), and the absence of CD according to the ratio of peri-dome choroidal thickness (CT) to sub-dome CT. Overall, no significant difference was found in age, AL, best corrected visual acuity (BCVA), dome base, dome height and choroidal vascularity among the three patterns of CD. However, the eyes with SDCD showed the thickest CT and the largest total choroidal area and vascular area.

Conclusions: Three morphological patterns of CD were found in highly myopic eyes with DSM. These three patterns should be considered when discussing CT in highly myopic eyes.
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http://dx.doi.org/10.1080/02713683.2019.1708955DOI Listing
August 2020

Three-year outcomes of macular buckling for macular holes and foveoschisis in highly myopic eyes.

Acta Ophthalmol 2020 Jun 19;98(4):e470-e478. Epub 2019 Nov 19.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: To assess the functional and structural outcomes of macular buckling using a silicone sponge-titanium exoplant for the treatment of foveoschisis (FS) and full-thickness macular holes (FTMHs) in highly myopic eyes.

Methods: Forty-nine consecutive patients with high myopia who underwent macular buckling for the treatment of FS and FTMHs were included. The outcomes measured included the anatomical success rate with FS resolution, retinal reattachment, MH closure, best corrected visual acuity (BCVA), axial length (AL) and complications of surgery. Moreover, the correlations between the BCVA at year three and series of factors, including age, duration of symptoms, baseline BCVA, AL, surgical type, preoperative macular status and severity of myopic maculopathy, were analysed.

Results: This study involved 28 patients (28 eyes) with FS and 21 patients (21 eyes) with FTMHs with macular detachment. Retinal reattachment was achieved in 100% of cases, while MH closure was achieved in 76.19% of cases. The BCVA significantly improved one year after macular buckling in the FS cases and two years after macular buckling in the FTMH cases, and it remained stable throughout the rest of the follow-up period. The mean AL decreased by 2.09 mm postoperatively. No major perioperative complications were observed, although one patient needed to explant the buckling device due to intolerable diplopia.

Conclusion: Macular buckling with a silicone sponge-titanium exoplant may represent a safe and effective surgical option for the treatment of FS and FTMH in highly myopic eyes. Macular buckling showed a high closure rate and virtually no tendency to recur.
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http://dx.doi.org/10.1111/aos.14305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318260PMC
June 2020

Comparison of macular buckling and vitrectomy for the treatment of macular schisis and associated macular detachment in high myopia: a randomized clinical trial.

Acta Ophthalmol 2020 May 17;98(3):e266-e272. Epub 2019 Nov 17.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Objective: To compare the efficacy and safety of macular buckling and vitrectomy for myopic traction maculopathy showing macular schisis (MS) and associated macular detachment (MD) but without full-thickness macular hole (FTMH).

Design: Prospective, randomized, parallel, open-label study.

Methods: Patients were randomly assigned to either buckling or vitrectomy group. Macular buckling and intravitreal C3F8 gas injection were performed in the buckling group. Small gauge vitrectomy, internal limiting membrane peeling (ILMP) and C3F8 gas tamponade were performed in the vitrectomy group. The patients were followed for 12 months.

Main Outcome Measures: Best-corrected visual acuity (BCVA) at 12 months.

Results: A total of 85 patients were randomized, 80 eyes were included (41 receiving buckling, 39 received vitrectomy), and 78 patients completed the study. There were less eyes determined as surgical failure and required a second surgery in the buckling group than vitrectomy the group (2.4% versus 18.4%, p = 0.021). After surgery, macular buckling achieved more improvement in BCVA (+21.7 versus +4.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p = 0.002). FTMH development was observed in only 1 (2.4%) eye, after removing of the implant due to recurrent conjunctival erosion, in the buckling group and 10 (26.3%) eyes (seven with-, three without MD) in the vitrectomy group (p < 0.001). More eyes developed cataracts in the vitrectomy group than did in the buckling group (28.9% versus 7.5%, p = 0.014). Macular buckling-associated strabismus (esotropia), binocular diplopia and implant exposure were observed in limited cases.

Conclusions And Relevance: Macular buckling is superior to vitrectomy with ILM peeling plus gas injection for surgical treatment of MS and associated MD in high myopia.
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http://dx.doi.org/10.1111/aos.14260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216842PMC
May 2020

Generation of human induced pluripotent stem cell lines from a patient with ITM2B-related retinal dystrophy and a non mutated brother.

Stem Cell Res 2019 12 5;41:101625. Epub 2019 Nov 5.

INSERM, CNRS, Institut de la Vision, Sorbonne Université, 17 rue Moreau, Paris, F-75012, France; CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, 28 rue de Charenton, Paris, F-75012, France. Electronic address:

Human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts of a patient affected with an autosomal dominant retinal dystrophy carrying the mutation c.782A>C, p.Glu261Ala in ITM2B and from an unaffected brother. Three different iPSC lines were generated and characterized from primary dermal fibroblasts of the affected subject and two from the unaffected brother. All iPSC lines expressed the pluripotency markers, were able to differentiate into the three germ layers and presented normal karyotypes. This cellular model will provide a powerful tool to study this retinal dystrophy and better understand the role of ITM2B.
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http://dx.doi.org/10.1016/j.scr.2019.101625DOI Listing
December 2019

Licorice isoliquiritigenin-encapsulated mesoporous silica nanoparticles for osteoclast inhibition and bone loss prevention.

Theranostics 2019 9;9(18):5183-5199. Epub 2019 Jul 9.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Mesoporous silica nanoparticles (MSNs) are extensively used in bone tissue regeneration and local drug delivery. However, the effects of MSNs alone on osteoclast formation and function, as well as the utilization of MSNs to deliver natural molecules against bone resorption, remain unexplored. Here, we report the development of licorice-derived bioactive flavonoid isoliquiritigenin (ISL)-encapsulated MSNs (MSNs-ISL) as a potent bone-bioresponsive nanoencapsulation system for prevention of osteoclast-mediated bone loss and . : We synthesized MSNs-ISL and then investigated the drug loading and release characteristics of the resulting nanoparticles. experiments on osteoclast differentiation and bone resorption were performed using mouse primary bone marrow-derived macrophages (BMMs). animal experiments were conducted using a lipopolysaccharide (LPS)-mediated calvarial bone erosion model. : The resulting MSNs-ISL were spherical and highly monodispersed; they possessed a large specific surface area and superior biocompatibility, and allowed acid-sensitive sustained drug release. Compared with free ISL and MSNs alone, MSNs-ISL significantly and additively inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast generation, decreased the size and quantity of sealing zones, and reduced the osteolytic capacity of osteoclasts . MSNs-ISL treatment also downregulated RANKL-stimulated mRNA expression of osteoclast-associated genes and transcription factors. Mechanistically, MSNs-ISL remarkably attenuated the RANKL-initiated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of mitogen-activated protein kinases (MAPKs), and phosphorylation and degradation of inhibitor of κBα (IκBα), together with the nuclear translocation of nuclear factor-κB (NF-κB) p65 and the activator protein (AP)-1 component c-Fos. Moreover, MSNs-ISL almost completely restrained the expression of nuclear factor of activated T cells (NFATc1). Consistent with the results, MSNs-ISL could block osteoclast activity; relieve inflammation-related calvarial bone destruction ; and suppress c-Fos, NFATc1, and cathepsin K expression levels. : Licorice ISL-encapsulated MSNs exhibit notable anti-osteoclastogenetic effects and protect against inflammatory bone destruction. Our findings reveal the feasibility of applying MSNs-ISL as an effective natural product-based bone-bioresponsive nanoencapsulation system to prevent osteoclast-mediated bone loss.
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http://dx.doi.org/10.7150/thno.33376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691588PMC
August 2020

MiR-361-5p inhibits cell proliferation and induces cell apoptosis in retinoblastoma by negatively regulating CLDN8.

Childs Nerv Syst 2019 08 3;35(8):1303-1311. Epub 2019 Jun 3.

Department of Dermatology, The First People's Hospital of Lianyungang, No. 182 tongtongbei Road, Haizhou District, Lianyungang, 222000, Jiangsu, China.

Purpose: MiR-361-5p has been reported to act as tumor suppressor in several types of cancers. Retinoblastoma (RB) is the most common ocular tumor in childhood. The current study aimed to investigate the expression pattern and biological function of miR-361-5p in RB.

Methods: Quantitative real time was utilized to determine and compare the expression of miR-361-5p in RB cells and normal retinal pigment epithelial cell line ARPE-19. CCK-8 and Edu assay were performed to assess cell proliferation. Cell apoptosis was evaluated using flow cytometry assay. Bioinformatics databases and luciferase reporter assay were applied to predict and confirm the target gene of miR-361-5p in RB cells.

Results: Here, we found miR-361-5p was significantly downregulated in RB cells compared with normal retinal pigment epithelial cell line ARPE-19. MiR-361-5p overexpression significantly inhibited or silencing promoted cell proliferation in Y79 and SO-RB50 cells, respectively. Flow cytometry assay showed a significantly decreased cell apoptosis in miR-361-5p silencing Y79 cells and increased cell apoptosis in miR-361-5p overexpressing SO-RB50 cells. Moreover, miR-361-5p directly bound to the 3' untranslated region of claudin 8 (CLDN8) and inhibited the expression of CLDN8. Furthermore, we found knockdown of CLDN8 photocopied the effect of miR-361-5p on cell proliferation and apoptosis in RB cells.

Conclusion: These results indicated that overexpression of miR-361-5p might act as a suppressor in RB by targeting CLDN8 to inhibit the cellular function.
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http://dx.doi.org/10.1007/s00381-019-04199-9DOI Listing
August 2019

A Pilot Clinical Study of Intravitreal Injection of Artesunate for Ocular Neovascularization.

J Ocul Pharmacol Ther 2019 06 15;35(5):283-290. Epub 2019 May 15.

1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

To evaluate the efficacy and primary safety of treatment with artesunate in reducing ocular neovascularization in humans. Five patients with corneal, iris, and retinal neovascularization and no light perception were treated with intravitreal injections of artesunate 80 μg. Visual acuity, anterior segment photography, fundus fluorescein angiography, and optical coherence tomography were used to evaluate efficacy, while intraocular pressure (IOP) and lens opacity degree were employed to evaluate safety. The primary endpoint was attenuation of neovascularization as determined at 24 weeks, with the last posttreatment follow-up at 52 weeks. Corneal and iris neovascularization, which were secondary to fundus ischemic diseases and retinal neovascularization in all 5 patients, were attenuated after 1 or 2 injections by the 52-week follow-up. Retinal neovascularization was also attenuated, and papilledema was alleviated. The average IOP fell from 25.5 mmHg to 17.66 mmHg. This pilot study determined that intravitreal artesunate injection is efficacious for reducing corneal, iris, and retinal neovascularization. These results indicate that this drug may be a novel alternative to the currently popular antivascular endothelial growth factor drugs used to suppress ocular neovascularization and improve visual function.
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http://dx.doi.org/10.1089/jop.2018.0097DOI Listing
June 2019

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next-generation sequencing.

Clin Exp Ophthalmol 2019 Sep 30;47(7):925-936. Epub 2019 May 30.

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China.

Background: The microRNAs (miRNA) have been found to play an important role in the pathogenesis of diabetic retinopathy. We try to explore the miRNA and piwi-interacting RNA (piRNA) profile in the aqueous humour of proliferative diabetic retinopathy (PDR) using next-generation sequencing (NGS).

Methods: Aqueous humour samples were collected from nine PDR eyes and nine cataract control eyes, and NGS was performed. Quantitative polymerase chain reaction (qPCR) was used to validate the sequencing results. An oxygen-induced retinopathy (OIR) model was used to validate the angiogenesis related miRNA.

Results: In total, 484 miRNAs were differently expressed between the PDR eyes and cataract control eyes, including 210 mature miRNAs and 274 novel miRNAs. Furthermore, eight miRNAs and 30 piRNAs were identified as the most differently expressed between the two groups (P > .85). This differential expression of miRNA was predicted to regulate Rho protein signal transduction, neurotransmitter uptake and histone lysine methylation. Relative expression patterns of miR-184, -150-5p and -93-5p were confirmed by qPCR. A reduced expression of miR-93-5p was confirmed in the OIR model.

Conclusions: This study comprehensively demonstrated the miRNA and piRNA expression profile of the aqueous humour of PDR eyes, which may serve as a potential biomarker and involved in the pathogenesis of PDR.
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http://dx.doi.org/10.1111/ceo.13554DOI Listing
September 2019

Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription.

J Cell Mol Med 2019 05 19;23(5):3345-3356. Epub 2019 Mar 19.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Objectives: This study focused on investigating the expression and underlying molecular mechanism of early growth response 1 (Egr1) in diabetic retinopathy.

Methods: A microarray assay was applied to examine differentially expressed genes in the retina tissues of normal rats, as well as in those of streptozotocin-induced diabetic rats. Human retinal vascular endothelial cells (HRVECs) transfected with sh-NC, sh-Egr1 or sh-Egr1+ pVax1-p53 were cultured under high-glucose conditions and then used to explore the role of Egr1 in vitro. The effect of Egr1 on retinal vascular dysfunction caused by diabetes was examined by sh-Egr1 administration in vivo RESULTS: Early growth response 1 was found to be up-regulated in the retinas of diabetic rats compared to those of normal rats. Down-regulation of Egr1 in HRVECs under high-glucose conditions inhibited the apoptosis, migration and tube formation in vitro. Moreover, sh-Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function by decreasing apoptotic cells and microvascular formation in vivo. The reduction of Egr1 evidently down-regulated the p53 expression. Overexpression of p53 rescued the inhibition of sh-Egr1 in HRVECs under high-glucose concentration on apoptosis, migration and tube formation in vitro.

Conclusion: Down-regulation of Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function via inhibiting p53 expression.
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http://dx.doi.org/10.1111/jcmm.14225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484413PMC
May 2019

Clinical observation of treatment of idiopathic macular hole with internal limiting membrane transplantation combined with temporal flap turnover and air filling.

Panminerva Med 2019 12 4;61(4):501-504. Epub 2019 Mar 4.

Department of Ophtalmology, The First People's Hospital of Lianyungang, Lianyungang, China -

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http://dx.doi.org/10.23736/S0031-0808.19.03611-5DOI Listing
December 2019

MORPHOLOGICAL CHARACTERISTICS AND VISUAL ACUITY OF HIGHLY MYOPIC EYES WITH DIFFERENT SEVERITIES OF MYOPIC MACULOPATHY.

Retina 2020 Mar;40(3):461-467

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: To investigate the morphological feature, visual acuity, and prevalence of macular complications in highly myopic eyes with different categories of myopic maculopathy (MM) according to the META-PM classification system.

Methods: The clinical records of 1,132 consecutive patients (1,841 eyes) with high myopia (refractive error ≤ -6D and axial length ≥26.5 mm), who visited the High Myopia Clinic at the Zhongshan Ophthalmic Center from January 2014 to July 2017, were reviewed. Fundus photograph, optical coherence tomography, axial length, refractive error, and best-corrected visual acuity were measured in each patient. Myopic maculopathy was graded from fundus photographs according to the META-PM classification, including tessellated fundus (C1), diffuse chorioretinal atrophy (C2), patchy atrophy (C3), and macular atrophy (C4). Other macular complications, including foveoschisis, extrafoveal schisis, full-thickness macular hole, epiretinal membrane, lacquer cracks, Fuchs spot, choroidal neovascularization, macular hemorrhage, and dome-shaped macula, were also investigated.

Results: Among the 1,841 eyes, 58 (3.15%) had no MM (C0), 779 (42.31%) had tessellated fundus only (C1), 524 (28.46%) had diffuse chorioretinal atrophy (C2), 352 (19.12%) had patchy chorioretinal atrophy (C3), and 128 (6.95%) had macular atrophy (C4). Age increased and best-corrected visual acuity became worse with the severity of MM (P < 0.01). Axial length was significantly longer with the severity of MM from C0 to C3 (P < 0.01), and spherical equivalent was greater with the severity of MM from C0 to C3 (P < 0.01) but was not different between C3 and C4 (P > 0.05). Subfoveal and parafoveal choroidal thicknesses were significantly thinner from C0 to C3 (P < 0.01). However, no significant difference was found between C3 and C4 in parafoveal choroidal thickness (P > 0.05). The complications were different among C0 to C4 correlated with MM (P < 0.01). The complications of foveoschisis, choroidal neovascularization, hemorrhage, lacquer cracks, Fuchs spot, dome-shaped macula, and epiretinal membrane were different between C1 and C2 (P < 0.01), but none of the complications were different between C3 and C4 (P > 0.05) except Fuchs spot (P = 0.009).

Conclusion: The morphological and functional characteristics in eyes with high myopia were positively correlated with the severity of C0 to C3 MM. However, no morphological difference was found between C3 and C4. The absence of the progressive relationship between C3 and C4 might be determined.
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http://dx.doi.org/10.1097/IAE.0000000000002418DOI Listing
March 2020

Two different initial treatment regimens of ranibizumab in myopic choroidal neovascularization: 12-month results from a randomized controlled study.

Clin Exp Ophthalmol 2019 03 22;47(2):250-258. Epub 2018 Nov 22.

State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Importance: The optimal treatment regimen for myopic choroidal neovascularization (mCNV) is essential to understand but currently poorly studied.

Background: To date, there is still no consensus on the optimal dosage and frequency of anti-vascular endothelial growth factor injections in treating mCNV.

Design: A prospective, single-centre, single-blind, randomized controlled study.

Participants: Adult patients with active mCNV.

Methods: Patients were randomized 1:1 to one or three doses initial ranibizumab treatments. Additional injections were administered pro re nata (prn) over 12 mo.

Main Outcome Measures: Number and frequency of injections.

Results: Fifty patients participated in the study. Patients in both 1 + prn or 3 + prn groups experienced similar best-corrected visual acuity gain and anatomical improvement, including central retinal thickness (CRT), CNV thickness, area of CNV and area of leakage. Over 12 mo, patients in the 1 + prn group received fewer ranibizumab injections (2.04 ± 1.22) compared with the 3 + prn group (3.58 ± 0.72, P<0.0001), but no statistic difference of the injection received was observed in the prn period. During the follow-up, 15 of 26 eyes in the 1 + prn group and 10 of 24 eyes in the 3 + prn group received additional injections after initial dosing (P = 0.2575). Cox regression analysis showed that 1 + prn, female, age > 55 y and CRT > 300 μm are risk factors for retreatment.

Conclusions And Relevance: The eyes with a single loading dose achieved parallel anatomical and functional visual improvement, while required less injections over 1 y. The risk factors for retreatment include 1 + prn, female, older age and thick retina thickness.
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http://dx.doi.org/10.1111/ceo.13424DOI Listing
March 2019

Implicit Emotion Regulation Deficits in Trait Anxiety: An ERP Study.

Front Hum Neurosci 2018 28;12:382. Epub 2018 Sep 28.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

According to the framework of emotion regulation (ER), both explicit and implicit forms are essential to our well-being. It is the interaction between these two processes that ensures adaptive emotional responses. Although many studies have focused on explicit ER deficits in anxiety, there is still a lack of awareness about the implicit form and its role in anxiety. To address this issue, we explored the time course of implicit ER processes in individuals with high and low trait anxiety (LTA). To do this, we employed the newly developed Priming-Identify (PI) paradigm, which includes a word-matching task (externally-generated implicit goals) and a facial expression identification task (emotion processing). We aimed to modulate the implicit ER goals of individuals through the application of different priming conditions (ER-related and -unrelated words). In addition to their behavioral effects, we recorded the influence of these priming conditions through event-related potentials (ERPs) during the facial expression identification task. Three ERP components were chosen as indexes of three stages of implicit ER processing: N170, early posterior negativity (EPN) and late positive potential (LPP). In individuals with LTA, the early N170 and the middle EPN were enlarged under the ER-related priming condition, while the LPP was not influenced. However, in individuals with high trait anxiety (HTA), we observed an absence of any significant differences between the ER-related and -unrelated priming conditions across all three ERP components. Furthermore, enlargements of N170 and EPN amplitudes were significantly correlated with a decrease in negative emotion experience scores. Our results suggest that HTA individuals experience implicit ER deficits during the early and middle stages of ER.
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http://dx.doi.org/10.3389/fnhum.2018.00382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172322PMC
September 2018

COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

Retina 2020 Jan;40(1):33-40

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: To compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment.

Methods: The current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups.

Results: The primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months.

Conclusion: The RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.
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http://dx.doi.org/10.1097/IAE.0000000000002348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924933PMC
January 2020

Two Paired Box 6 mutations identified in Chinese patients with classic congenital aniridia and cataract.

Mol Med Rep 2018 Nov 10;18(5):4439-4445. Epub 2018 Sep 10.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.

Congenital aniridia is a rare genetic disorder characterized by a variable degree of hypoplasia or absence of iris. It is frequently associated with keratopathy, cataract, juvenile‑onset glaucoma and foveal and optic nerve hypoplasia. Mutations in the Paired Box 6 (PAX6) gene on chromosome 11p13 have been demonstrated to cause aniridia. The aim of the present study was to investigate the genetic variations of PAX6 in two sporadic patients from southern China with classic congenital aniridia and cataract. Complete ophthalmic and physical examinations were performed, including best‑corrected visual acuity, intraocular pressure, slit‑lamp examination, fundus examination, optical coherence tomography, ultrasound biomicroscopy, and Pentacam scanning. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two patients, their unaffected parents and 200 unrelated control subjects from the same population. Exons 4‑13 of the PAX6 gene were amplified by polymerase chain reaction and sequenced directly. Patient 1 was affected with aniridia accompanied by congenital cataract and nystagmus. A novel heterozygous PAX6 frameshift mutation c.277delG (p.Glu93SerfsX31) in exon 6 was identified in this patient. Patient 2 was presented with aniridia, congenital cataract, lens subluxation and glaucoma. A recurrent nonsense mutation c.718C>T (p.Arg240X) in exon 9 was identified in this patient. The present results expand the mutation spectrum of PAX6 and will be valuable for genetic counseling in the affected families. Additionally, the identification of these mutations reiterates the importance of PAX6 in ocular development and sheds light on the pathogenesis of congenital aniridia.
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http://dx.doi.org/10.3892/mmr.2018.9469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172400PMC
November 2018

Collagen-Hydroxypropyl Methylcellulose Membranes for Corneal Regeneration.

ACS Omega 2018 Jan 30;3(1):1269-1275. Epub 2018 Jan 30.

School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.

To improve intraocular transparency of collagen matrices, hydroxypropyl methylcellulose (HPMC) was introduced for the first time into cross-linked collagen to form collagen-HPMC composite membranes. Light transmittance and refractive indices of the membranes are enhanced by incorporation of HPMC in comparison to the control of cross-linked collagen membranes. Maximum light transmittance of the collagen-HPMC membrane was up to 92%. In addition, their permeability of nutrients such as glucose, tryptophan, and NaCl was superior or comparable to that of human corneas. In vitro results demonstrated that the collagen-HPMC membrane supported adhesion and proliferation of human corneal epithelial cells (HCECs), showing good cytocompatibility to HCECs. The corneas maintained a smooth surface and clear stroma postoperatively after 7 months of implantation of collagen-HPMC membranes into the corneas of rabbits. The good intraocular biocompatibility was verified by maintaining a high optical clarity for over 6 months after transplantation. Hematoxylin and eosin staining results showed the growth of stromal keratocytes into the collagen-HPMC implants, indicating the ability of the collagen-HPMC membrane to induce corneal cell regeneration. Taken together, the collagen-HPMC membrane might be a promising candidate for use in corneal repair and regeneration.
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http://dx.doi.org/10.1021/acsomega.7b01511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044638PMC
January 2018

Targeted next‑generation sequencing identifies two novel COL2A1 gene mutations in Stickler syndrome with bilateral retinal detachment.

Int J Mol Med 2018 Oct 4;42(4):1819-1826. Epub 2018 Jul 4.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.

Stickler syndrome is a group of inherited connective tissue disorders characterized by distinctive facial and ocular abnormalities, hearing loss and early‑onset arthritis. The aim of the present study was to investigate the genetic changes in two Chinese patients with Stickler syndrome, manifested as bilateral retinal detachment and peripheral retinal degeneration. Complete ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination and fundus examination, were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the patients, their unaffected family members and 200 unrelated control subjects from the same population. Next‑generation sequencing of established genes associated with ocular disease was performed. A heterozygous collagen type II α1 chain (COL2A1) mutation c.1310G>C (p.R437P) in exon 21 was identified in Family 1 and a heterozygous COL2A1 mutation c.2302‑1G>A in intron 34 was identified in Family 2. The functional effects of the mutations were assessed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT) analysis. The c.1310G>C mutation was predicted to damage protein structure and function, and the c.2302‑1G>A mutation was predicted to result in a splicing defect. The findings of the current study expand the established mutation spectrum of COL2A1, and may facilitate genetic counseling and development of therapeutic strategies for patients with Stickler syndrome.
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http://dx.doi.org/10.3892/ijmm.2018.3752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108863PMC
October 2018

Re: Laíns et al.: Human plasma metabolomics study across all stages of age-related macular degeneration identifies potential lipid biomarkers (Ophthalmology. 2018;125:245-254).

Ophthalmology 2018 07;125(7):e45-e46

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2018.02.025DOI Listing
July 2018

Procyanidins attenuate neuropathic pain by suppressing matrix metalloproteinase-9/2.

J Neuroinflammation 2018 Jun 21;15(1):187. Epub 2018 Jun 21.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Background: Management of neuropathic pain is a real clinical challenge. Despite intense investigation, the mechanisms of neuropathic pain remain substantially unidentified. Matrix metalloproteinase (MMP)-9 and MMP-2 have been reported to contribute to the development and maintenance of neuropathic pain. Therefore, inhibition of MMP-9/2 may provide a novel therapeutic approach for the treatment of neuropathic pain. In this study, we aim to investigate the effect of procyanidins (PC), clinically used health product, on MMP-9/2 in neuropathic pain.

Methods: The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in mice. Cell signaling was assayed using gelatin zymography, western blotting, and immunohistochemistry. The BV2 cells were cultured to investigate the effects of PC on microglia.

Results: Both in vitro and in vivo administration of PC significantly suppresses the activity of MMP-9/2. Oral administration of PC relieves neuropathic pain behaviors induced by chronic constriction sciatic nerve injury (CCI) in mice. Additionally, PC blocks the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppresses CCI-induced MAPK phosphorylation and neuronal and microglia activation, including the reduced phosphorylation of protein kinase C γ and NMDAR1. Furthermore, PC decreases the phosphorylation of p38 mitogen-activated protein kinase and inhibits the translocation of nuclear factor-κB (NF-κB) in microglia.

Conclusions: PC is an effective and safe approach to alleviate neuropathic pain via a powerful inhibition on the activation of MMP-9/2.
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http://dx.doi.org/10.1186/s12974-018-1182-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013948PMC
June 2018