Publications by authors named "Xuanchu Duan"

38 Publications

The potential role of long noncoding RNAs in primary open-angle glaucoma.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 10. Epub 2021 Jul 10.

Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, China.

Purpose: To identify the potential genes in human trabecular meshwork (TM) related to primary open-angle glaucoma (POAG).

Methods: First, long noncoding RNA (LncRNA) and mRNA expression profiles in TM samples from 4 control subjects and 4 POAG patients were accessed by microarray analyses. Then, twenty lncRNAs were validated by real-time quantitative PCR in the same samples from microarray analyses. Finally, eight highly expressed lncRNAs were further tested by real-time quantitative PCR in TM from 8 normal controls and 19 POAG patients. Expression data were normalized and analyzed using the R software. Pathway analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results: A total of 2179 lncRNAs and 923 mRNAs in the TM of POAG patients were significantly upregulated, and 3111 lncRNAs and 887 mRNAs were significantly downregulated. ENST00000552367, ENST00000582505, ENST00000609130, NR_029395, NR_038379, and ENST00000586949 expression levels were significantly higher in the TM from a different cohort of POAG patient than normal controls.

Conclusion: ENST00000552367, ENST00000582505, ENST000006091- 30, NR_029395, NR_038379, and ENST00000586949 may play essential roles in the development of POAG.
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http://dx.doi.org/10.1007/s00417-021-05279-wDOI Listing
July 2021

Analysis of the Responsiveness of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in the Treatment of OAG/OHT Patients.

J Ophthalmol 2021 25;2021:5586719. Epub 2021 May 25.

Department of Ophthalmology, Changsha Aier Eye Hospital, Changsha, Hunan, China.

Aim: Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety.

Methods: A literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation.

Results: Eleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs.

Conclusion: The existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.
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http://dx.doi.org/10.1155/2021/5586719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169256PMC
May 2021

A PITX2 splice-site mutation in a family with Axenfeld-Rieger syndrome leads to decreased expression of nuclear PITX2 protein.

Int Ophthalmol 2021 Apr 25;41(4):1503-1511. Epub 2021 Jan 25.

Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Purpose: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder characterized by ocular anterior segment abnormalities. In the current study, we describe clinical and genetic findings in a Chinese ARS pedigree.

Methods: An ARS pedigree was recruited and patients were given comprehensive ophthalmic examinations and general physical examinations. DNA from the proband II:2 was used for exome sequencing. Sanger sequencing was utilized to identify and validate PITX2 variations. qPCR and western blotting were performed to detect PITX2 expression in immortalized peripheral blood lymphocytes.

Results: All affected family members showed typical ocular abnormalities, including iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. They also exhibited systemic anomalies, such as microdontia, hypodontia, and redundant periumbilical skin. A heterozygous splice-site variation c.390 + 1G > A in PITX2, which might lead to a truncated PITX2 protein (p.Val131IlefsX127), was found in the proband. Sanger sequencing validated that the variation completely co-segregated with the ARS phenotype within this family and was absent in 100 unrelated controls. Western blotting revealed that the nuclear PITX2 protein was significantly decreased in patients compared with controls. Nonetheless, there was no significant difference in the total PITX2 protein level, consistent with qPCR results showing no alteration in PITX2 mRNA levels in the patient group.

Conclusions: PITX2 c.390 + 1G > A (p.Val131IlefsX127) was a novel genetic etiology of the ARS pedigree. The mutation leads to decreased nuclear PITX2, indicating lower transcriptional activity.
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http://dx.doi.org/10.1007/s10792-021-01704-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035109PMC
April 2021

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

Can J Ophthalmol 2021 Jan 21. Epub 2021 Jan 21.

The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.

Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.

Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.

Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.
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http://dx.doi.org/10.1016/j.jcjo.2020.12.010DOI Listing
January 2021

Posterior staphyloma is associated with the microvasculature and microstructure of myopic eyes.

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

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.

Objective: To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS).

Methods: This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters.

Results: The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE.

Conclusions: PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.
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http://dx.doi.org/10.1007/s00417-020-05057-0DOI Listing
January 2021

Tear Film Instability and Meibomian Gland Dysfunction Correlate with the Pterygium Size and Thickness Pre- and Postexcision in Patients with Pterygium.

J Ophthalmol 2019 3;2019:5935239. Epub 2019 Dec 3.

Aier School of Ophthalmology, Central South University, Changsha 410000, China.

Purpose: This study aimed to evaluate the effects of excision on dry eye and meibomian gland dysfunction (MGD) in individuals with pterygium, before and after surgery. It also aimed to investigate how these effects correlate with the size and thickness of the pterygium.

Subjects And Methods: 63 eyes from 63 patients with primary nasal pterygium and 45 eyes from 45 healthy volunteers without ocular pathologies were enrolled in this study. 63 eyes from 63 patients underwent pterygium surgery. ImageJ software was used to calculate the pterygium size based on images of the anterior segments. Anterior segment spectral domain optical coherence tomography (SD-OCT) was performed preoperatively to measure the thickness of the pterygium 1 mm anterior to the nasal scleral spur. The ocular surface disease index (OSDI), Schirmer I Test (SIT), and MGD grade were used to evaluate the eyes, and the eyes were imaged using the noninvasive keratograph average tear film breakup time (NIBUTav), tear meniscus height (TMH), meiboscore, and lipid layer grading tools of the Oculus® Keratograph 5M, preoperatively and at 1, 3, and 6 months postoperatively.

Results: The OSDI, NIBUTav, lid margin abnormality, meiboscore, and lipid layer grading values differed significantly in the pterygium patients in comparison with the controls ( < 0.01 for all scores). However, the SIT and TMH values were unchanged between the two groups (all > 0.05). Multivariate regression analysis demonstrated that the NIBUTav, meiboscore, and lipid layer grading score was significantly correlated with the pterygium parameters, such as size and thickness. The postoperative OSDI, NIBUTav, lid margin abnormality, and lipid layer grading values improved significantly ( < 0.05 for all scores). The SIT, TMH, and meiboscore results did not differ significantly between the pre- and postoperative values ( > 0.05). Among the conventional and automated indexes, at 1 month postoperatively, SIT and TMH were significantly correlated with the pterygium parameters, but no correlation was observed at 3 and 6 months postoperatively. The OSDI, NIBUTav, meiboscore, and lipid layer grading values at 1, 3, and 6 months postoperatively were significantly correlated with the pterygium parameters.

Conclusion: Abnormal tear film and meibomian gland (MG) function improved following pterygium excision in the patients with primary pterygium, which was associated with uncomfortable ocular symptoms. Pterygium parameters, such as size and thickness, correlated with the dry eye and MGD indexes in patients pre- and postoperatively, potentially offering a novel strategy for clinical implementation of pterygium excision surgery.
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http://dx.doi.org/10.1155/2019/5935239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914971PMC
December 2019

A novel glaucomatous representation method based on Radon and wavelet transform.

BMC Bioinformatics 2019 Dec 24;20(Suppl 25):693. Epub 2019 Dec 24.

The Second Xiangya Hospital of Central South University, Changsha, 410011, China.

Background: Glaucoma is an irreversible eye disease caused by the optic nerve injury. Therefore, it usually changes the structure of the optic nerve head (ONH). Clinically, ONH assessment based on fundus image is one of the most useful way for glaucoma detection. However, the effective representation for ONH assessment is a challenging task because its structural changes result in the complex and mixed visual patterns.

Method: We proposed a novel feature representation based on Radon and Wavelet transform to capture these visual patterns. Firstly, Radon transform (RT) is used to map the fundus image into Radon domain, in which the spatial radial variations of ONH are converted to a discrete signal for the description of image structural features. Secondly, the discrete wavelet transform (DWT) is utilized to capture differences and get quantitative representation. Finally, principal component analysis (PCA) and support vector machine (SVM) are used for dimensionality reduction and glaucoma detection.

Results: The proposed method achieves the state-of-the-art detection performance on RIMONE-r2 dataset with the accuracy and area under the curve (AUC) at 0.861 and 0.906, respectively.

Conclusion: In conclusion, we showed that the proposed method has the capacity as an effective tool for large-scale glaucoma screening, and it can provide a reference for the clinical diagnosis on glaucoma.
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http://dx.doi.org/10.1186/s12859-019-3267-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929399PMC
December 2019

LncRNA NR_003923 promotes cell proliferation, migration, fibrosis, and autophagy via the miR-760/miR-215-3p/IL22RA1 axis in human Tenon's capsule fibroblasts.

Cell Death Dis 2019 08 7;10(8):594. Epub 2019 Aug 7.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Noncoding RNAs (ncRNAs), including long ncRNAs (lncRNA) have manifested an important role in the pathophysiology of many diseases. Glaucoma is a primary cause of irreversible blindness worldwide. However, the involvement of lncRNAs in glaucoma remains largely unknown. Here, we performed the lncRNA expression assay based on clinical tissues and identified a specific functional lncRNA, NR_003923, and investigated its potential role in glaucoma. Knockdown of NR_003923 in human Tenon's capsule fibroblast cells (HTFs) inhibited TGF-β-induced cell migration, proliferation, fibrosis, and autophagy. The dual luciferase reporter assay confirmed that miR-760 and miR-215-3p interacted with NR_003923. miR-760 and miR-215-3p inhibitor reversed the effects of NR_003923 and TGF-β-induced cell apoptosis. Moreover, the expression of miR-760 and miR-215-3p was decreased in glaucoma comparing with control. Furthermore, through microarray we found IL22RA1 was increased in glaucoma and both of miR-760 and miR-215-3p bound to the 3' UTR of IL22RA1. Overexpression of IL22RA1 enhanced HTFs migration and proliferation, while miR-760 and miR-215-3p mimics reversed these promotive biological roles induced by IL22RA1. In conclusion, NR_003923 and IL22RA1 might contribute to glaucoma progression and be a novel and potential biomarkers and therapeutic targets for glaucoma.
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http://dx.doi.org/10.1038/s41419-019-1829-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685939PMC
August 2019

Effects of rosiglitazone/PHBV drug delivery system on postoperative fibrosis in rabbit glaucoma filtration surgery model.

Drug Deliv 2019 Dec;26(1):812-819

a Department of Ophthalmology, The Second Xiangya Hospital, Central South University , Changsha , Hunan Province , China.

The aim of this study is to investigate the effects and toxicities of poly(3-hydroxybutyric acid--3-hydroxyvaleric acid) (PHBV)-loading rosiglitazone on preventing scar formation after glaucoma filtration surgery (GFS) in the rabbit model. Rosiglitazone/PHBV drug delivery system was prepared via electrospinning. Release behavior of RSG/PHBV membrane was evaluated by high-performance liquid chromatography. The different concentration membranes were implanted under the conjunctiva of the rabbit's eyes (RSG/PHBV groups). Also, MMC-soaked sponges were placed under the conjunctiva of the eyes (positive group) for 3 min. Intraocular pressures and bleb features were then assessed for 4 weeks postoperative. Bleb sections were stained with HE, Masson's trichrome and α smooth muscle action (αSMA) immunohistochemistry. The protein expression of collagen I, αSMA, and connective tissue growth factor in the bleb area were then quantified. The following results were observed: (1) the concentration of rosiglitazone would not affect the morphology of RSG/PHBV membrane. (2) RSG/PHBV membrane would effective and safety prevent the formation of fibrosis after GFS in the rabbit model. Implantation of RSG/PHBV membrane prevents scar formation after GFS. What's more, it ameliorated toxicity to conjunctiva and cornea compared with the placement of MMC. The RSG/PHBV membrane would be a more effectivity and safer strategy than MMC.
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http://dx.doi.org/10.1080/10717544.2019.1648590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713170PMC
December 2019

Efficacy and safety of prostaglandin analogues in primary open-angle glaucoma or ocular hypertension patients: A meta-analysis.

Medicine (Baltimore) 2019 Jul;98(30):e16597

Department of Ophthalmology, Second Xiangya Hospital, Central South University.

Background: To evaluated and compared the efficacy and safety of 3 prostaglandin analogues (0.005% latanoprost, 0.004% travoprost, and 0.03% bimatoprost) in treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: PubMed, Embase, Cochrane library, Web of science, CNKI, Wanfang, and Vip database, published between January 1, 2000 and June 1, 2018, were systematically examined for randomized controlled trials (RCT) based on prostaglandin analogues for POAG or OHT treatment. Statistical analyses including weighted mean difference (WMD) calculation and odds ratio (OR) were performed using Review Manager Software version 5.3.

Result: The 17 studies were included in this analysis (N = 2433 participants) with 1∼12 months' follow-ups. The difference of intraocular pressure (IOP) reduction between latanoprost and travoprost group had not significant; there was significant difference of IOP reduction between latanoprost and bimatoprost group in the third month and sixth month; Travoprost was significantly different from bimatoprost in reducing IOP in the third month. Travoprost revealed an elevated risk of conjunctival hyperemia compared with latanoprost. An elevated risk of conjunctival hyperemia and growth of lashes compared with latanoprost. Bimatoprost shows lower ocular tolerability with higher incidence of side effects such as conjunctival hyperemia.

Conclusions: 0.03% bimatoprost appears more effective following long time use (3 and 6 month post-treatment) for IOP control compared to 0.005% latanoprost, and is more effective compared to 0.004% travoprost after being used for a certain period of time (3 months post-treatment); nevertheless, 0.005% latanoprost is better tolerated in patients with POAG or OHT.
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http://dx.doi.org/10.1097/MD.0000000000016597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709278PMC
July 2019

Rosiglitazone Treatment Prevents Postoperative Fibrosis in a Rabbit Model of Glaucoma Filtration Surgery.

Invest Ophthalmol Vis Sci 2019 06;60(7):2743-2752

Departments of Medicine, Ophthalmology, and Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, United States.

Purpose: To evaluate the potential antifibrotic effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor γ (PPARγ)-selective agonist, on subconjunctival fibrosis in a rabbit model of glaucoma filtration surgery (GFS) in vivo, and to investigate the underlying mechanisms in human Tenon's fibroblasts (HTFs) in vitro.

Methods: GFS were performed on adult male New Zealand white rabbits with chronic ocular hypertension previously established by injections of 2% methylcellulose into the anterior chamber. Rabbits were treated by RSG, mitomycin C (MMC) or 5-fluorouracil (5-FU) intraoperatively. The morphology of filtering blebs was evaluated by Indiana Bleb Appearance Grading Scale (IBAGS) scoring. Expression of profibrotic genes was determined by quantitative PCR, immunoblot, and/or histochemical analysis. In vitro studies were performed in a transforming growth factor (TGF)-β1-based cell model of fibrosis. Autophagy was evaluated by the formation of autophagosomes and autolysosomes using fluorescent and transmission electron microscopy and by expression of key mediators in the autophagic pathway.

Results: RSG treatment ameliorated a rebound intraocular pressure (IOP) elevation, prolonged the survival of filtering blebs, and attenuated subconjunctival fibrosis in rabbits following trabeculectomy. Pretreatment of HTFs with RSG inhibited TGF-β1-induced expression of profibrotic genes encoding specificity protein 1, connective tissue growth factor, and α smooth muscle actin. RSG augmented TGF-β1-induced autophagy in HTFs via a beclin1/VPS34-dependent mechanism. Augmentation of autophagy is associated with inhibition of TGF-β1-induced profibrotic gene expression by RSG.

Conclusions: RSG treatment prevents subconjunctival fibrosis after GFS by inhibition of profibrotic gene expression through a mechanism involved in promoting autophagy in local fibroblasts. RSG represents a novel antifibrotic drug with the potential to improve the success rate of GFS.
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http://dx.doi.org/10.1167/iovs.18-26526DOI Listing
June 2019

A novel frameshift mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome using targeted exome sequencing.

BMC Med Genet 2019 06 11;20(1):105. Epub 2019 Jun 11.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, People's Republic of China.

Background: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant genetic disorder that is characterized by specific abnormalities of the anterior segment of the eye. Heterozygous mutations in two developmental transcription factor genes PITX2 and FOXC1 have been identified within ARS patients, accounting for 40 to 70% of cases. Our purpose is to describe clinical and genetic findings in a Chinese family with ARS.

Methods: An ARS family with three affected members was recruited. The patients underwent a series of complete ophthalmologic examinations, general physical examination and dental radiography. DNA samples of proband II-1 were used for targeted exome sequencing of the FOXC1 and PITX2 genes. Sanger sequencing was used to validate the variation in PITX2. Quantitative real-time PCR was carried out to detect the expression of PITX2 in patients and normal controls.

Results: All affected members showed iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. In addition, they revealed systemic anomalies, including microdontia, hypodontia, and redundant periumbilical skin. A novel heterozygous frameshift variation, c.515delA, in PITX2 was found in the proband, which might lead to a truncated PITX2 protein (p.Gln172ArgfsX36). Sanger sequencing validated that the variation completely cosegregated with the ARS phenotype among this family, but was absent in 100 unrelated controls. Quantitative real-time PCR analysis revealed that the mRNA expression of PITX2 was significantly decreased in patients compared with that in unrelated normal controls.

Conclusions: PITX2 c.515delA (p.Gln172ArgfsX36) was the genetic etiology of our pedigree. The mutation led to decreased PITX2 gene expression and a truncated mRNA transcript.
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http://dx.doi.org/10.1186/s12881-019-0840-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560744PMC
June 2019

A case report of an extranodal NK/T-cell lymphoma nasal type, occurring primarily in eyes with masquerade syndrome.

Medicine (Baltimore) 2019 Mar;98(11):e14836

Department of Ophthalmology, The Second Xiangya Hospital.

Rationale: Extranodal natural killer T-cell lymphoma nasal type (ENKL) is an extremely rare tumor with a very low survival rate. In recent decades, only a few ENKL cases have been published. Presenting a special ENKL case lead the authors to emphasize the primary features of ENKL in early diagnosis and therapy. Here we report an unusual ENKL case which was initially found in the eyes and presented as masqueraded uveitis PATIENT CONCERNS:: A 55 years old female, with vision loss in the right eye for approximately 6 months, and vision blurry, redness and pain in the left eye for 2 weeks, was referred to our hospital.

Diagnosis: Clinical examinations and images demonstrated bilateral anterior uveitis, retinal and choroidal detachment, and secondary glaucoma. After 3 months, the patient began to present a sore throat, fever, and headaches. The computed tomography (CT) and magnetic resonance imaging (MRI) of her skull demonstrated nothing positive. One month later, a neoplasm was found in her nasopharynx and tonsil, which was confirmed, by histopathology, as ENKL INTERVENTIONS:: This patient was prescribed with steroid for 3 months because of the first diagnosis by the ophthalmologist. After the other symptoms like a sore throat, fever and headaches occurred, symptomatic treatment was given. Unfortunately, when the real cause was found, the patient could not tolerate the other treatment for ENKL.

Outcomes: Since the patient was treated with steroid without improvement, she died due to the septic shock and multiple organ failure.

Lessons: Clinicians should always be cautious to ENKL which can be easily be misdiagnosed in the early stage. Early diagnosis and appropriate treatment are keys to raise the survival rate of ENKL patients.
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http://dx.doi.org/10.1097/MD.0000000000014836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426616PMC
March 2019

Region-segmentation strategy for Bruch's membrane opening detection in spectral domain optical coherence tomography images.

Biomed Opt Express 2019 Feb 14;10(2):526-538. Epub 2019 Jan 14.

Changsha Aier Eye Hospital, Changsha 410015, China.

Bruch's membrane opening (BMO) is an important biomarker in the progression of glaucoma. Bruch's membrane opening minimum rim width (BMO-MRW), cup-to-disc ratio in spectral domain optical coherence tomography (SD-OCT) and lamina cribrosa depth based on BMO are important measurable parameters for glaucoma diagnosis. The accuracy of measuring these parameters is significantly affected by BMO detection. In this paper, we propose a method for automatically detecting BMO in SD-OCT volumes accurately to reduce the impact of the border tissue and vessel shadows. The method includes three stages: a coarse detection stage composed by retinal pigment epithelium layer segmentation, optic disc segmentation, and multi-modal registration; a fixed detection stage based on the U-net in which BMO detection is transformed into a region segmentation problem and an area bias component is proposed in the loss function; and a post-processing stage based on the consistency of results to remove outliers. Experimental results show that the proposed method outperforms previous methods and achieves a mean error of 42.38 μm.
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http://dx.doi.org/10.1364/BOE.10.000526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377878PMC
February 2019

Potential Biomarkers for Primary Open-Angle Glaucoma Identified by Long Noncoding RNA Profiling in the Aqueous Humor.

Am J Pathol 2019 04 22;189(4):739-752. Epub 2019 Jan 22.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, People's Republic of China. Electronic address:

This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, long noncoding RNA (lncRNA) and mRNA expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Coding-noncoding gene coexpression networks were drawn to predict potential lncRNA functions. lncRNA T267384, ENST00000607393, and T342877 expression levels were further tested by real-time quantitative PCR in AH from 29 POAG and 30 cataract patients, in iris tissues from 16 POAG patients and 10 controls, and in plasma from 49 POAG patients and 55 healthy controls. Finally, ENST00000607393 function was characterized in an in vitro model of cell calcification. A total of 3627 lncRNAs and 2228 mRNAs in the AH of POAG patients were significantly up-regulated, and 1520 lncRNAs and 820 mRNAs were significantly down-regulated. Seven lncRNAs showed positive correlation with glaucoma-associated gene, bone morphogenetic protein 2. Moreover, real-time quantitative RT-PCR confirmed that T267384, ENST00000607393, and T342877 expression levels were significantly higher in the AH from a different cohort of POAG patients. ENST00000607393 was also significantly higher in the iris and plasma of POAG patients. Last, ENST00000607393 knockdown alleviated calcification of primary human trabecular meshwork cells in vitro. Therefore, lncRNAs T267384, ENST00000607393, and T342877 may be potential biomarkers for POAG diagnosis. ENST00000607393 might be a new therapeutic target for trabecular meshwork calcification.
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http://dx.doi.org/10.1016/j.ajpath.2018.12.011DOI Listing
April 2019

Ocular pulse amplitude in different types of glaucoma using dynamic contour tonometry: Diagnosis and follow-up of glaucoma.

Exp Ther Med 2017 Nov 30;14(5):4148-4152. Epub 2017 Aug 30.

Department of Ophthalmology, Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China.

The aim of the present study was to compare the ocular pulse amplitude (OPA) in patients with different types of glaucoma using dynamic contour tonometry (DCT), to evaluate ocular and systemic factors associated with the OPA and to verify whether OPA measured by DCT is an independent predictor for glaucoma diagnosis. A total of 217 eyes of 217 participants in the following five groups were included in this cross-sectional study: Chronic angle closure glaucoma (CACG), primary open angle glaucoma, normal tension glaucoma (NTG), suspected open angle glaucoma (SOAG) and normal control (NC). The following tests were simultaneously performed during a single visit: Intra-ocular pressure (IOP), OPA, cup-to-disk (C/D) ratio, mean damage (MD) and loss variance (LV). OPAs were compared in each group. The association between OPA and IOP, age, C/D ratio, MD and LV was detected. OPA analysis prior to and after trabeculectomy was also performed to assess its prognostic value. Among the 217 individuals, the OPA was consistent with the IOP, both measured by DCT, along with the MD and LV. Patients with CACG and SOAG had higher OPA values than those with NTG and normal controls. Compared with patients aged >30 years, the OPA was significantly lower in younger patients, while they may not have been affected by different C/D ratios. After trabeculectomy, the OPA had significantly decreased compared with the values prior to surgery. In conclusion, the present study showed that the OPA is correlated with the IOP determined by DCT. CACG and SOAG patients had higher OPA values than patients with other types of glaucoma. OPA measured by DCT may be a predictor for glaucoma diagnosis and prognosis.
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http://dx.doi.org/10.3892/etm.2017.5074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658696PMC
November 2017

Patient satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution: a survey study in patients with glaucoma in China.

Patient Prefer Adherence 2017 28;11:845-852. Epub 2017 Apr 28.

Allergan plc, Shanghai, People's Republic of China.

Background: Poor adherence to treatment is a problem in glaucoma, and patient dissatisfaction with topical glaucoma medication is a barrier to adherence. The objective of this study was to evaluate glaucoma patients' satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution (BTFC).

Methods: This observational, multicenter study was conducted in China in adults with glaucoma treated with BTFC for 1-3 months. Five hundred patients answered a questionnaire concerning their demographic characteristics, history of glaucoma and topical glaucoma treatment, and use of BTFC. The primary endpoint was patient satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10= very satisfied).

Results: Patients received BTFC alone (65%) or with other treatments (35%), most commonly a carbonic anhydrase inhibitor. Most patients (87%) used BTFC as a replacement for other medication, usually a β-blocker or prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for initiating BTFC therapy were poor efficacy of previous treatment (72% of patients) and side effects of previous treatment (32% of patients). Most patients agreed or very much agreed that BTFC provided better control of intraocular pressure (85% of patients), had a simpler administration (87% of patients), and was associated with better tolerance and comfort (82% of patients) compared with their previous treatment. Mean satisfaction scores were significantly higher for BTFC than for previous treatments among all patients (7.8 versus 6.0; <0.0001) and within patient subgroups based on demographic characteristics, pattern of BTFC use, and previous treatment.

Conclusion: Patients were highly satisfied with BTFC used alone or concomitantly with another topical medication. Patients previously treated with a β-blocker, prostaglandin analog, carbonic anhydrase inhibitor, α-adrenergic agonist, or combination of two medications were more satisfied with BTFC than with their previous treatment. Most reported that intraocular pressure control, tolerability, and ease of administration improved with BTFC.
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http://dx.doi.org/10.2147/PPA.S131853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417666PMC
April 2017

Anisotropic Finite Element Modeling Based on a Harmonic Field for Patient-Specific Sclera.

Biomed Res Int 2017 7;2017:6073059. Epub 2017 Feb 7.

School of Information Science and Engineering, Central South University, Changsha, Hunan 410083, China.

. This study examined the influence of anisotropic material for human sclera. . First, the individual geometry of patient-specific sclera was reproduced from a laser scan. Then, high quality finite element modeling of individual sclera was performed using a convenient automatic hexahedral mesh generator based on harmonic field and integrated with anisotropic material assignment function. Finally, comparison experiments were designed to investigate the effects of anisotropy on finite element modeling of sclera biomechanics. . The experimental results show that the presented approach can generate high quality anisotropic hexahedral mesh for patient-specific sclera. . The anisotropy shows significant differences for stresses and strain distribution and careful consideration should be given to its use in biomechanical FE studies.
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http://dx.doi.org/10.1155/2017/6073059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320077PMC
March 2017

mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic nerve ischemia.

Sci Rep 2016 11 25;6:37805. Epub 2016 Nov 25.

Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

The therapeutic potential of targeting CD4+Foxp3+ regulatory T cells (Tregs) remains controversial under the condition of neuroinflammation. This study aims to explore the neuroprotective role of Tregs in optic nerve ischemia (ONI) and evaluate the therapeutic strategy of Tregs transfer with a focus on targeting the mammalian target of rapamycin (mTOR) pathway. Intraocular pressure was transiently increased in adult C57BL/6 mice to induce ONI. Mucosal tolerance of myelin basic protein (MBP) markedly increased retinal ganglion cell (RGC) survival after ONI through enhanced Tregs suppression. mTOR inhibition significantly promoted the frequency of MBP-immunized Tregs in vitro with increased production of anti-inflammatory cytokines. Transient rapamycin treatment highly promoted the immunosuppressive capacity of Tregs and inhibited retinal inflammation in ONI animals. Intravenous infusion of MBP-immunized Tregs, instead of regular Tregs, beneficially modulated immune activities of host retinal CD11b+ cells and CD4+ effector T cells, leading to significant improvement of RGC survival. Importantly, rapamycin treatment further enhanced the neuroprotective effect of Tregs transfer. Taken together, these findings reveal a fine regulation of mTOR signaling on immunized Tregs after acute retinal injury. Adoptive transfer with targeting-mTOR strategy markedly improves neuronal recovery after ONI, supporting the therapeutic potentials of Tregs in acute and chronic neurological disorder.
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http://dx.doi.org/10.1038/srep37805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122903PMC
November 2016

Retinal vessel segmentation in colour fundus images using Extreme Learning Machine.

Comput Med Imaging Graph 2017 01 30;55:68-77. Epub 2016 May 30.

School of Information Science and Engineering, Central South University, Changsha, China; Mobile Health Ministry of Education-China Mobile Joint Laboratory, Changsha, China. Electronic address:

Attributes of the retinal vessel play important role in systemic conditions and ophthalmic diagnosis. In this paper, a supervised method based on Extreme Learning Machine (ELM) is proposed to segment retinal vessel. Firstly, a set of 39-D discriminative feature vectors, consisting of local features, morphological features, phase congruency, Hessian and divergence of vector fields, is extracted for each pixel of the fundus image. Then a matrix is constructed for pixel of the training set based on the feature vector and the manual labels, and acts as the input of the ELM classifier. The output of classifier is the binary retinal vascular segmentation. Finally, an optimization processing is implemented to remove the region less than 30 pixels which is isolated from the retinal vascilar. The experimental results testing on the public Digital Retinal Images for Vessel Extraction (DRIVE) database demonstrate that the proposed method is much faster than the other methods in segmenting the retinal vessels. Meanwhile the average accuracy, sensitivity, and specificity are 0.9607, 0.7140 and 0.9868, respectively. Moreover the proposed method exhibits high speed and robustness on a new Retinal Images for Screening (RIS) database. Therefore it has potential applications for real-time computer-aided diagnosis and disease screening.
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http://dx.doi.org/10.1016/j.compmedimag.2016.05.004DOI Listing
January 2017

Suppression of Type I Collagen Expression by miR-29b Via PI3K, Akt, and Sp1 Pathway, Part II: An In Vivo Investigation.

Invest Ophthalmol Vis Sci 2015 Sep;56(10):6019-28

Purpose: We investigated the efficacy of miR-29b in inhibiting scar formation in rabbits who undergo glaucoma filtering surgery (GFS).

Methods: Trabeculectomy was performed on 60 rabbits diagnosed with glaucoma. The rabbits were divided into 5 groups: a blank group, single surgery group, positive control group that was treated with intraoperative mitomycin C (MMC), negative control group that was treated twice with empty vector postoperatively, and experimental group that was treated twice with Lentivirus-mediated miR-29b after being subjected to trabeculectomy. The operated eyes were tracked and followed up from postoperative days 1 to 28 (D1-D28). After the surgery, real-time PCR and Western blot analysis were performed on D28.

Results: At 1 week after undergoing GFS, the IOP was significantly lower in the eyes having filtering blebs. No statistically significant difference was found in the four treatment groups. After 21 days, the filtering bleb function score of the experimental group was the highest; however, their IOP was the lowest. On postoperative D28, the mean number of fibroblasts in the experimental group was significantly the lowest. The experimental group had the least collagen content according to Sircol assay. In the experimental group, the level of Col1A1 expression also was reduced in the sclera and conjunctival areas.

Conclusions: A subconjunctival injection of lentivirus-mediated miR-29b lowers postoperative IOP and sustains the function of filtering bleb. It inhibits the proliferation of fibroblasts and reduces collagen deposition by repressing the PI3K/Akt/Sp1 pathway in rabbits subjected to GFS.
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http://dx.doi.org/10.1167/iovs.15-16558DOI Listing
September 2015

[Application of anti-VEGF agents in treatment of neovascular glaucoma and anti-scarring in filtering surgery].

Authors:
Xu Jia Xuanchu Duan

Zhonghua Yan Ke Za Zhi 2015 Apr;51(4):314-8

Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; Email:

Neovascular glaucoma (NVG) is a group of secondary glaucoma which led by a variety of diseases that have anoxia or ischemia to the retina. Some studies have found that the etiology was related to the vascular endothelial growth factor (VEGF). At present, anti-VEGF as a treatment method to NVG, has become an important advance in the field of glaucoma research, which established a new way to improve the prognosis. This review mainly focused on the pathophysiologic basis and clinical research of NVG, fundamental research and applications about four kinds of anti-VEGF agents (Bevacizumab, Ranibizumab, Pegaptanib and Aflibercept) and application of treatment of NVG and anti-scarring in filtering surgery. The review also provided references for the clinical treatment of NVG and improving the success rate of operation.
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April 2015

Bilateral impending macular holes after a high-voltage electrical shock injury and its surgical outcome: a case report.

J Med Case Rep 2014 Dec 2;8:399. Epub 2014 Dec 2.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, China.

Introduction: A macular hole is a rare complication after high-voltage electrical shock injury and only a few cases have been reported to date. To the best of our knowledge, this is the first report of bilateral impending macular holes after high-voltage electrical shock.

Case Presentation: We report a case of bilateral impending macular holes in a 39-year-old male Chinese patient who sustained a high-voltage electrical shock three months prior to presentation. Our patient complained of gradually diminished eyesight in both eyes, with visual acuity of 20/100 and 20/40 in his right and left eyes respectively. Our patient underwent pars plana vitrectomy accompanied by octafluoropropane gas and triamcinolone acetonide injections, and was discharged from our hospital with slightly improved vision.

Conclusion: The visual outcome of impending macular holes caused by high-voltage electrical shock may be poor despite tissue residue at the fovea and surgical intervention aimed at aiding macular recovery. Surgery is, however, effective in the short term in restoring normal anatomical macular structure.
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http://dx.doi.org/10.1186/1752-1947-8-399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289027PMC
December 2014

Heat shock protein 72 confers protection in retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model.

Neural Regen Res 2014 Jul;9(14):1395-401

Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Optic nerve transection increased the expression of heat shock protein 72 (HSP72) in the lateral geniculate body, indicating that this protein is involved in the prevention of neuronal injury. Zinc sulfate and quercetin induced and inhibited the expression of HSP72, respectively. Intraperitoneal injections of zinc sulfate, SP600125 (c-Jun N-terminal kinase inhibitor), or quercetin were performed on retinal ganglion cells in a Wistar rat model of chronic ocular hypertension. Our results showed that compared with the control group, the expression of HSP72 in retinal ganglion cells and the lateral geniculate body was increased after the injection of zinc sulfate, but was decreased after the injection of quercetin. The expression of phosphorylated c-Jun N-terminal kinases and phosphorylated c-Jun were visible 3 days after injection in the control group, and reached a peak at 7 days. Zinc sulfate and SP600125 significantly decreased the expression of p-c-Jun, whereas quercetin significantly enhanced the expression of this protein. These results suggest that HSP72 protects retinal ganglion cells and lateral geniculate body in a rat model of chronic ocular hypertension from injury by blocking the activation of the stress-activated kinase/c-Jun N-terminal kinase apoptotic pathway.
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http://dx.doi.org/10.4103/1673-5374.137595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160872PMC
July 2014

MIR34A regulates autophagy and apoptosis by targeting HMGB1 in the retinoblastoma cell.

Autophagy 2014 Mar 3;10(3):442-52. Epub 2014 Jan 3.

Department of Ophthalmology; The Second Xiangya Hospital; Central South University; Hunan, China.

MIR34A (microRNA 34a) is a tumor suppressor gene, but how it regulates chemotherapy response and resistance is not completely understood. Here, we show that the microRNA MIR34A-dependent high mobility group box 1 (HMGB1) downregulation inhibits autophagy and enhances chemotherapy-induced apoptosis in the retinoblastoma cell. HMGB1 is a multifaceted protein with a key role in autophagy, a self-degradative, homeostatic process with a context-specific role in cancer. MIR34A inhibits HMGB1 expression through a direct MIR34A-binding site within the HMGB1 3' untranslated region. MIR34A inhibition of HMGB1 leads to a decrease in autophagy under starvation conditions or chemotherapy treatment. Inhibition of autophagy promotes oxidative injury and DNA damage and increases subsequent CASP3 activity, CASP3 cleavage, and PARP1 [poly (ADP-ribose) polymerase 1] cleavage, which are important to the apoptotic process. Finally, upregulation of MIR34A, knockdown of HMGB1, or inhibition of autophagy (e.g., knockdown of ATG5 and BECN1) restores chemosensitivity and enhances tumor cell death in the retinoblastoma cell. These data provide new insights into the mechanisms governing the regulation of HMGB1 expression by microRNA and their possible contribution to autophagy and drug resistance.
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http://dx.doi.org/10.4161/auto.27418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077883PMC
March 2014

Posttraumatic cavernous hemangioma of the skull.

J Craniofac Surg 2014 Jan;25(1):e48-51

From the Department of Ophthalmology, 2nd Xiangya Hospital of Central South University, Changsha, China.

A 59-year-old man presented with a slowly enlarging mass in the lateral orbital rim of the left eye for 1 year. He also reported a history of crania defect in the left front bone (6 years earlier) which was confirmed on the former computed tomographic (CT) scan. On examination, the solid mass lesion located in the left frontal extends to the lateral orbital rim of the left eye. CT scan showed a mass with poorly defined margins, which invaded the neighboring tissue and nearly damaged the bone, and located on the exact site of the preceding crania defect. Complete resection was performed, and the clinical diagnosis of cavernous hemangioma was confirmed on histopathologic examination. Skull cavernous hemangiomas are rare tumors for which the origin is not yet clear. We report a case in which the intraosseous hemangiomas developed at the same site of the preceding crania defect.
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http://dx.doi.org/10.1097/SCS.0b013e3182a2eec0DOI Listing
January 2014

Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells.

Neural Regen Res 2013 Feb;8(4):320-7

Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.
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http://dx.doi.org/10.3969/j.issn.1673-5374.2013.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107537PMC
February 2013

Primary synovial sarcoma in the orbit.

J AAPOS 2012 Dec 14;16(6):582-4. Epub 2012 Nov 14.

Department of Ophthalmology, 2nd Xiangya Hospital, Central South University, China.

Synovial sarcoma is a rare malignant neoplasm that accounts for approximately 6% to 9% of all soft-tissue tumors. It occurs predominately in upper and lower extremities of young adults. We report the first case of a primary orbital synovial sarcoma in an 18-month-old girl.
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http://dx.doi.org/10.1016/j.jaapos.2012.09.002DOI Listing
December 2012

Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human Tenon's fibroblasts.

Invest Ophthalmol Vis Sci 2012 Mar 26;53(3):1670-8. Epub 2012 Mar 26.

Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China.

Purpose: To evaluate the expression profile of microRNAs (miRNAs) and their roles in human Tenon's fibroblasts (HTFs), and to establish an miRNA-based gene-silencing method for antifibrosis in vitro.

Methods: The miRNA expression profile was analyzed by microarray using quiescent and transforming growth factor beta 1 (TGFβ1)-stimulated primary HTFs, respectively. Candidate miRNAs were identified by quantitative RT-PCR. miRNAs potentially targeting fibrosis-related genes were predicted using a published algorithm. Predicted fibrosis-related genes regulated by candidate miRNAs were confirmed by transfection of the miRNA into HTF culture (with or without TGFβ1 treatment), followed by quantitative RT-PCR and Western blot analysis.

Results: In all, 38 miRNAs were identified to be upregulated and 31 downregulated, in TGFβ1-stimulated HTFs. Among those, the miR-29b, downregulated in TGFβ1-treated HTFs, targeted a cadre of mRNAs that encode proteins involved in fibrosis, including PI3Kp85α, Sp1, and collagen type I alpha1 (Col1A1). Treatment of HTFs with TGFβ1 activated the PI3K/Akt/Sp1 pathway and, consequently, induced an increase in the expression of type I collagen. Overexpression of miR-29b inhibited the PI3K/Akt/Sp1 pathway, and attenuated the expression of Col1A1. CONCLUSIONS. miR-29b acted as a suppressor of type I collagen gene by repressing the PI3K/Akt/Sp1 pathway in HTFs. Overexpression of miR-29b protected subconjunctival tissues against collagen production and fibrosis. These findings provided a novel rationale for the development of miRNA-based strategies for attenuating scar formation after glaucoma filtering surgery.
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http://dx.doi.org/10.1167/iovs.11-8670DOI Listing
March 2012

Rosiglitazone attenuates activation of human Tenon's fibroblasts induced by transforming growth factor-β1.

Graefes Arch Clin Exp Ophthalmol 2012 Aug 4;250(8):1213-20. Epub 2012 Jan 4.

Department of Ophthalmology, People's Hospital of Hebei Province, Hebei, Shijiazhuang, 050051, People's Republic of China.

Purpose: To investigate the influence of rosiglitazone on activation of human Tenon's fibroblasts (HTFs) and to access the possible mechanism.

Methods: Cultured human Tenon's fibroblasts were pretreated in two different concentrations of rosiglitazone (5 μmol/l and 10 μmol/l) before being stimulated with 5 ng/ml transforming growth factor β1 (TGF-β1). The viability and proliferation of cells were accessed by cell count kit-8 assay; Cell migration was examined by the wound closure assay; Alpha smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) and type I collagen (COL I) transcription were detected by RT-qPCR; The expression and localization of α-SMA protein were examined by Western-blot analysis and Immunofluorescence staining; Western-blot analysis was also used to check the expression of CTGF, COL I peroxisome proliferator-activated receptor gamma (PPAR-γ), and phosphorylation of the signaling protein Smad2/3

Results: Rosiglitazone is able to attenuate the up-regulation of α-SMA, CTGF, and COL I transcription, as well as affect protein expression, proliferation, and migration of cells; rosiglitazone also can increase PPAR-γ expression and attenuate Smad2/3 phosphorylation.

Conclusions: Rosiglitazone can effectively attenuate activation of HTFs induced by TGF-β1 without obvious toxicity. The possible mechanism might be that rosiglitazone interferes with TGF-β/Smad signaling pathway.
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http://dx.doi.org/10.1007/s00417-011-1903-6DOI Listing
August 2012
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