CXC- receptor 2 promotes extracellular matrix production and attenuates migration in peripapillary human scleral fibroblasts under mechanical strain.

As the main loading-bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell-5000™ tension system. We found that CXC- ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2-STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling.

Identification of key genes and pathways in scleral extracellular matrix remodeling in glaucoma: Potential therapeutic agents discovered using bioinformatics analysis.

Background: Glaucoma is a leading cause of irreversible blindness. Remodeling of the scleral extracellular matrix (ECM) plays an important role in the development of glaucoma. The aim of this study was to identify the key genes and pathways for the ECM remodeling of sclera in glaucoma by bioinformatics analysis and to explore potential therapeutic agents for glaucoma management. Methods: Genes associated with glaucoma, sclera and ECM remodeling were detected using the text mining tool pubmed2ensembl, and assigned Gene Ontology (GO) biological process terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the GeneCodis program. A protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape, module analysis was performed using the Molecular Complex Detection (MCODE) plugin, and GO and KEGG analyses of the gene modules were performed using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The genes that clustered in the significant module were selected as core genes, and functions and pathways of the core genes were visualized using ClueGO and CluePedia. Lastly, the drug-gene interaction database was used to explore drug-gene interactions of the core genes to find drug candidates for glaucoma. Results: We identified 125 genes common to "Glaucoma", "Sclera", and "ECM remodeling" by text mining. Gene functional enrichment analysis yielded 30 enriched GO terms and 20 associated KEGG pathways. A PPI network that included 60 nodes with 249 edges was constructed, and three gene modules were obtained using the MCODE. We selected 13 genes that clustered in module 1 as core candidate genes that were associated mainly with ECM degradation and cell proliferation and division. The HIF-1 signaling pathway, FOXO signaling pathway, PI3K-Akt signaling pathway and TGFB signaling pathway were found to be enriched. We found that 11 of the 13 selected genes could be targeted by 26 existing drugs. Conclusions: The results showed that VEGFA, TGFB1, TGFB2, TGFB3, IGF2, IGF1, EGF, FN1, KNG1, TIMP1, SERPINE1, THBS1, and VWF were potential key genes involved to scleral ECM remodeling. Furthermore, 26 drugs were identified as potential therapeutic agents for glaucoma treatment and management.

Current and Emerging Technology for Continuous Glucose Monitoring.

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.

Quality of life of glaucoma patients in China: sociodemographic, clinical, and psychological correlates-a cross-sectional study.

PURPOSE: To assess vision-related quality of life (VRQoL) in Chinese glaucoma patients and explore its sociodemographic, clinical and psychological correlates, and determine which of them explain the largest variation. METHODS: This cross-sectional study included 508 Chinese glaucoma patients. Chinese-version Glaucoma Quality of Life-15 questionnaire (CHI-GQL-15) and Hospital Anxiety and Depression Scales were administered to all participants to evaluate their VRQoL and psychological distresses. Visual functions (habitual-corrected visual acuity (HCVA), intraocular pressure, and mean defect (MD) of visual field) were assessed through clinical examinations by professionals. Sociodemographic information and other treatment histories were collected via interviews and chart review. Stepwise multiple linear regression analyses were performed to identify sociodemographic, clinical, and psychological predictors of VRQoL. RESULTS: The mean summary score for CHI-GQL-15 was 28.79 ± 12.74. Patients exhibited the greatest difficulty in activities involving glare and dark adaptation (28.19 ± 22.86), followed by central and near vision (26.18 ± 26.56), peripheral vision (18.03 ± 21.37), and the least difficulty for outdoor mobility (15.06 ± 24.57). Moderate and heavy economic burden, HCVA and MD of both the better and the worse eyes, number of glaucoma surgeries in the treatment history and the presence of depression were independent predictors for VRQoL of glaucoma patients. Clinical factors explained the largest variation. CONCLUSION: VRQoL of glaucoma patients is multifactorial and was primarily determined by clinical indices. VRQoL assessment could be informative when adopted as a complement to objective visual measures in clinical practice.

Linguistic and psychometric validation of the Chinese version of the Glaucoma Quality of Life-15 (GQL-15-CHI): a cross-sectional study.

BACKGROUND: Maintaining glaucoma patients' quality of life (QoL) has become one of the most important goals for treatments. The purpose of this study is to develop a Chinese version of Glaucoma Quality of Life-15 item Questionnaire (GQL-15-CHI), and examine its psychometric properties. METHODS: The Glaucoma Quality of Life-15 item Questionnaire (GQL-15) was translated and culturally adapted into Chinese, and administered to glaucoma patients recruited from Shanghai Eye and ENT Hospital. Visual functions: habitual-corrected visual acuity (HCVA), intraocular pressure (IOP), and mean defect (MD) of visual field) were assessed through clinical examination by professionals. Sociodemographic and other clinical data were collected via interviews and chart review. According to Nelson's glaucoma staging system, patients were stratified as mild, moderate, and severe visual field loss (VFL). The psychometric properties, including internal consistency, test-retest reliability, item-scale correlations and factor analysis were conducted. The divergent validity was assessed through bilateral comparisons of the GQL-15-CHI composite and subscale scores between patients of different VFLs after controlling for potential confounders. RESULTS: A total of 508 glaucoma patients were recruited (male: 265, female: 243). The mean age was 55.41 years. The Cronbach's α coefficients ranged from 0.75 to 0.91 for the subscales. The test-retest reliability, as estimated by the intraclass correlation coefficients, were above 0.70 for all subscales. Statistically significant differences were showed in the GQL-15-CHI summary and subscale scores after controlling for sociodemographic and clinical confounders (P < 0.05) among patients with different VFLs. CONCLUSION: The GQL-15-CHI showed psychometric properties comparable to those of the original English version, and thus could be used as a reliable and valid tool for assessment of QoL in Chinese glaucoma patients.

Interaction of copolymer-1-activated T cells and microglia in retinal ganglion cell protection.

BACKGROUND: The interaction of copolymer-1-activated T cells and microglia on retinal ganglion cells survival in vitro was explored. METHODS: Copolymer-1-specific T cells were made by repeated copolymer-1 stimulation of T cells, microglia were isolated from the retinas of newborn rats, and then, they were co-cultured (the experimental group) for 48 h. Retinal ganglion cells were collected from the retinas of adult rats, purified, and then, the supernatants from different groups were added. After 72 h, terminal-deoxynucleotidyl transferase-mediated d-UTP nick end labelling analysis was used to observe retinal ganglion cell apoptosis, and reverse transcription polymerase chain reaction was used to test messenger RNA expression of Caspase-3 and Caspase-8. The levels of cytokines, including insulin-like growth factor-1, brain-derived neurotrophic factor, tumour necrosis factor-α and interleukin-10, in the supernatants were examined by enzyme-linked immunosorbent assay to explore the possible mechanisms undergoing. RESULTS: After 72 h, the mean retinal ganglion cell apoptosis rate in the experimental group was the lowest (25.36%) among the groups. The messenger RNA expression of Caspase-3 and Caspase-8 in this group was significantly lower than that of the control groups (both P < 0.05). The secretion of interlekin-10 and brain-derived neurotrophic factor, insulin-like growth factor-1 and tumour necrosis factor-α in the supernatant of the experimental group were higher than that of the control groups (both P < 0.05) after co-culture. CONCLUSIONS: The interaction of copolymer-1-specific T cells with microglia could reduce retinal ganglion cell apoptosis. The related immune mechanisms were complicated. Upregulation of brain-derived neurotrophic factor and insulin-like growth factor-1, and the balance of some pro-inflammatory and anti-inflammatory cytokines may be involved in this protective autoimmunity.

Effects of combined phacoemulsification and viscogoniosynechialysis versus trabeculectomy in patients with primary angle-closure glaucoma and coexisting cataract.

AIMS: To compare the effectiveness of combined phacoemulsification and viscogoniosynechialysis versus trabeculectomy alone in primary angle-closure glaucoma (PACG) with a coexisting cataract. METHODS: Thirty-nine Chinese patients (39 eyes) were retrospectively analyzed: 19 patients underwent combined phacoemulsification and viscogoniosynechialysis (group 1), and 20 underwent trabeculectomy (group 2). In both groups, the intraocular pressure (IOP), the number of antiglaucoma medications, the best corrected visual acuity (BCVA), the central anterior chamber depth (ACD), the synechial/apposition angle closure (SAC), and the success rates were assessed. RESULTS: The median follow-up periods were similar for both groups (10 months). At the last follow-up, the mean IOP was 14.09 ± 6.89 mm Hg and the mean number of antiglaucoma medications was 0.36 ± 0.59 in group 1; in group 2, the mean IOP was 16.48 ± 4.74 mm Hg (p = 0.066) and the mean number of antiglaucoma medications was 1.05 ± 0.99 (p = 0.025). In terms of the mean central ACD and the mean SAC, there were significant differences between the groups (p = 0.0000, respectively). Kaplan-Meier analysis revealed that the cumulative probability of success in group 1 was higher than that in group 2 (p = 0.0051). CONCLUSION: Compared to trabeculectomy, combined phacoemulsification and viscogoniosynechialysis resulted in a lower requirement for glaucomatous medications, a greater improvement in BCVA, and a higher cumulative probability that treatment would be successful among patients with PACG and coexisting cataracts.

[Expressional changes of Th1 and Th2 cells in retina of a rat glaucoma model vaccinated by Cop-1].

OBJECTIVE: To explore the morphological and expressional changes of Th1 cells and Th2 cells in retina of a rat model of glaucoma vaccinated by Cop-1 (Copolymer-1) and elucidate the possible neuroprotection roles played by Th1/Th2. METHODS: After modeling, the aqueous outflow from the right eyes was blocked by a ligation of three of four episcleral veins. There were 48 rats with elevated IOP (intraocular pressure) immunized by Cop-1 (Cop-1 group), 48 rats with elevated IOP immunized by PBS (phosphate-buffered saline) (PBS group) and 10 rats without any treatment (normal group). The experimental rats were immunized with Cop-1/PBS emulsified in a total volume of 0.4 ml complete Freund's adjuvant. The immunization was administered subcutaneously at the base of tail. Immunofluorescence was employed to test the distribution and activation of Th1 and Th2 cells in retina at Days 3, 7, 10, 17, 24 and 31 post-immunization respectively for each group. Western blot was selectively performed according to the results of immunofluorescence to verify if there was a similar variation of the retinal expression of IL-4 protein. RESULTS: The results of immunofluorescence showed the numbers of Th1 cells peaked at Day 7 in both Cop-1 ((216 ± 21)/mm(2)) and PBS groups ((194 ± 27)/mm(2)). And no statistical significance existed between two groups (P > 0.05). The numbers of Th2 cells in the experimental groups peaked at Day 7 with statistical significance (Cop-1 group: 300 ± 28/mm(2) vs PBS group: 129 ± 27/mm(2)) (P < 0.01). With the prolongation of experimental period, the number of Th2 cells decreased gradually in the Cop-1 group but remained greater than that of the PBS group afterward (P < 0.05). The Western blot results showed that the expression of IL-4 in the Cop-1 group (1.91 ± 0.05) was significantly higher than that of the PBS group (0.51 ± 0.04) from Day 3 and peaked at Day 7 (2.11 ± 0.06 vs 0.57 ± 0.05). Then the IL-4 expression decreased gradually in the COP-1 group but still represented statistical significance versus the PBS group until Day 31 post-immunization (P < 0.001). CONCLUSION: The retinal activation and accumulation of IL-4 are found in a rat model of chronic glaucoma immunized by Cop-1. Thus Th2 cells may play vital roles in the Cop-1-induced neuroprotective autoimmune responses.

[Study on changes of intraocular pressure within 24 hours in primary open angle glaucoma and normal eyes].

OBJECTIVE: To analyze the discipline of intraocular pressure (IOP) variation, through circadian intraocular pressure monitoring in primary open-angle glaucoma (POAG) patients and normal controls, with a view to provide basis for individualized treatment of glaucoma. METHODS: Subjects were enrolled from the outpatients of Shanghai Beizhan Hospital and Eye and ENT Hospital of Fudan University, which were diagnosed as primary open angle glaucoma, from April 2006 to April 2009. Totally there were 102 cases of patients and 83 cases of normal volunteers. All the subjects accepted 24-hour IOP measurements using non-contact tonometer every two hours starting from 8:00 am. And the IOP between 00:00 to 06:00 am was measured in sitting position immediately after wake up. RESULTS: The differences of peak IOP [(16.0 ± 2.7) mm Hg of right eye and (16.2 ± 2.7) mm Hg of left eye in normal group; (25.3 ± 5.6) mm Hg of right eye and (24.8 ± 5.1) mm Hg of left eye in POAG group], valley IOP (11.1 ± 2.5) mm Hg of right eye and (11.0 ± 2.3) mm Hg of left eye in normal group; (16.3 ± 3.7) mm Hg of right eye and (16.2 ± 3.3) mm Hg of left eye in POAG group, average IOP (13.4 ± 2.5) mm Hg of right eye and (13.4 ± 2.5) mm Hg of left eye in normal group; (19.9 ± 4.3) mm Hg of right eye and (19.8 ± 3.8) mm Hg of left eye in POAG group), and IOP fluctuations (5.0 ± 1.6) mm Hg of right eye and (5.2 ± 1.7) mm Hg of left eye in normal group; (9.1 ± 3.6) mm Hg of right eye and (8.6 ± 3.8) mm Hg of left eye in POAG group between two groups were all of statistically significance (P < 0.01). Notably, the peak IOP of 59.6% in normal control group and 73.5% in POAG group were outside working hours, especially in the time period from 00:00 to 06:00 am. The peak value of 50% in normal group and 64.7% in POAG group located between 00:00 to 06:00 in the morning. CONCLUSIONS: By comparison and analysis, 24-hour intraocular pressure measurement could provide us pre-treatment basic state, so as to provide detailed information for individualized treatment. If possible, it is suggested that 24-hour IOP monitoring should be added as a routine examination of primary open angle glaucoma.

Impact of binocular visual field loss on driving performance in glaucoma patients.

AIM: To evaluate the driving performance in young and middle-aged Chinese glaucoma patients with mild to severe visual field loss compared to those without glaucoma by using a driving simulation test. METHODS: Twenty-nine participants were included in this study: nine patients with glaucoma but pass the binocular Esterman visual field test, ten patients with glaucoma and fail the binocular Esterman visual field test, and ten age-matched healthy controls. A driving simulation test was designed as a frequency-based analysis of a lane-keeping task. The total performance error, the control-response amplitude and delay were calculated. RESULTS: Esterman visual field test fail group showed the longest delay of control-response among three groups (P=0.02). And the delay in lane-keeping task was significantly associated with inferior field of better-eye (r=0.51, P=0.004) and integrated visual field (r=0.55, P=0.002). CONCLUSION: Young and middle-aged glaucoma patients with binocular visual field loss suffered from a longer delay of response in driving simulation test, while inferior visual field having more impact than superior visual field.

Mechanical Strain Regulates Myofibroblast Differentiation of Human Scleral Fibroblasts by YAP.

Scleral extracellular matrix (ECM) remodeling is thought to play a critical role in the pathogenesis of glaucoma. Mechanical strain induced by elevated intraocular pressure can promote myofibroblast differentiation of fibroblasts and result in scleral ECM remodeling; however, the underlying mechanism remains poorly understood. Yes-associated protein (YAP) is a mechanosensory protein and the key downstream transcriptional effector of the Hippo signaling pathway. Here, we investigated the role of YAP in mechanical strain-induced myofibroblast transformation during glaucoma scleral ECM remodeling. Integrative bioinformatics analyses were performed to identify the key pathways for the ECM remodeling of the sclera in glaucoma. Sprague-Dawley rats were used to establish a chronic ocular hypertension model, and the expression of collagen type I (COL1) and YAP in the sclera was analyzed by immunohistochemical analysis and Western blotting. Furthermore, human scleral fibroblasts (HSFs) were cultured and subjected to mechanical strain. In groups with or without the YAP siRNA or YAP inhibitor, cell proliferation, migration capacity, and the expression levels of YAP, COL1, and α-smooth muscle actin (α-SMA) were evaluated by Cell Counting Kit-8 assay, scratch assay, and Western blotting. The interactions between YAP and Smad3 were demonstrated by coimmunoprecipitation, and the expression levels of COL1 and α-SMA were evaluated in groups treated with or without the Smad3 inhibitor. We first revealed that the Hippo signaling pathway may be involved in mechanical strain-induced scleral ECM remodeling through bioinformatics analysis. Furthermore, the in vivo study showed upregulated YAP, COL1, and α-SMA expression in the hypertensive sclera of rats. In vitro, mechanical strain increased YAP and COL1 expression in HSFs and promoted myofibroblast differentiation. After YAP knockdown or inhibition with verteporfin, mechanical strain-induced fibrotic changes in HSFs were markedly suppressed. Additionally, YAP showed a protein interaction with Smad3, and the upregulation of a-SMA and COL1 in response to mechanical strain was also significantly downregulated following the inhibition of Smad3. In conclusion, mechanical strain activated scleral myofibroblast differentiation via YAP. The YAP pathway may play an important role in regulating scleral myofibroblast differentiation and ECM remodeling of the sclera in glaucoma.

The Dynamic Scleral Extracellular Matrix Alterations in Chronic Ocular Hypertension Model of Rats.

Intraocular pressure (IOP) generates stress and strains in the laminar cribrosa and sclera, which may affect the development and progression of glaucoma. Scleral stiffness and material components have changed under elevated IOP. However, the detailed changes of the components of the hypertensive sclera are not well understood. In this study, we aimed to investigate the changes of the main components in the scleral extracellular matrix (ECM), and matrix metalloproteinase 2 (MMP2) and their relationship with time under chronic elevated IOP in Sprague-Dawley rats. An ocular hypertension model was established in the right eyes by anterior chamber injection with 0.3% carbomer solution. The left eye was used as the contralateral control. Immunofluorescent imaging of the tissue frozen sections, Western blot analysis, and quantitative PCR (qPCR) were performed to detect the expressions of type I collagen (COL1), elastin, and MMP2 in the sclera. The ocular hypertension model was successfully established. As compared to the left eyes, the immunofluorescence imaging, Western blot analysis, and qPCR showed that COL1, elastin, and MMP2 were significantly increased in the right eyes at 1 week (all P < 0.05). At 2 weeks, COL1 in the right eyes tended to be lower than that in the left eyes, while elastin and MMP2 were still higher (all P < 0.05) in the right eyes. When the IOP was elevated for 4 weeks, both COL1 and MMP2 were lower than those in the left eyes (all P < 0.05), while elastin between the two eyes was similar (P > 0.05). Under this 4-week hypertensive state, COL1 and elastin were initially elevated at 1 week, and then obviously reduced from 2 to 4 weeks. Consistently, MMP2 was gradually increased, with a peak at 2 weeks, and then decreased at 4 weeks. In conclusion, the chronic elevated IOP induced dynamic scleral ECM alterations in rats in a pressure- and time-dependent manner. MMP2 may play an important role in the balance between ECM synthesis and degradation and could potentially be a novel target for glaucoma intervention.

[Trabeculotomy on primary congenital glaucoma: a retrospective study of 164 cases (257 eyes)].

OBJECTIVE: To study the relationship of long-term effect of trabeculotomy on primary congenital glaucoma and the related risk factors. METHOD: 164 consecutive patients with primary congenital glaucoma (257 eyes), underwent initial surgery of trabeculotomy between 1996 and 2007. Follow-up was conducted for 30.9 (8.6 - 58.3) months, with a follow-up rate of 89.02%. Multivariate analysis by Logistic regression was conducted to analyze the relation of the factors including age of onset, time between onset and operation, preoperative intraocular pressure, clarity of cornea, and corneal diameter to the failure of surgery. Cox proportional hazards regression modeling was used to analyze the factors related to success of surgery. RESULT: Multivariate logistic regression showed that the preoperative intraocular pressure (IOP) and clarity of cornea were independent risk factors for final outcome (OR(IOP) = 1.408, P = 0.047, and OR(CLA) = 1.691, P = 0.019). Cox regression showed that clarity of cornea was the factor related to the surgery success time (OR(CLA) = 1.632, P = 0.008). CONCLUSION: Clarity of cornea reflexes the condition of primary congenital glaucoma more stably than IOP. It is possible to prognosticate the surgical outcome to combine the clarity of cornea with the IOP value before operation.

[Clinical analysis on sixteen cases of Sturge-Weber syndrome-associated glaucoma].

OBJECTIVE: To investigate the clinical features of Sturge-Weber syndrome-associated glaucoma and its surgical treatment. METHODS: A retrospective case series study. The general clinical data and related ocular manifestations in 16 patients (21 eyes) with Sturge-Weber syndrome-associated glaucoma in our hospital from January 2003 to December 2007 were analyzed retrospectively. RESULTS: Age of the patients ranged between 1 month to 31 years old, and the median age was 11 years. Bilateral facial angiomas were present in 8 patients, and two of them had extensive hemangioma. Eleven cases had unilateral glaucoma and 3 of them had bilateral facial angiomas. Five patients had bilateral glaucoma and all of them had bilateral facial angiomas. Open anterior chamber angle was found in all affected eyes by gonioscopy. B-scan ultrasonography was performed in 21 eyes and diffused occupying lesions in the choroid were found in 8 eyes (38.1%). Posterior bowing of the iris, low echo in ciliary body and shallow ciliary body detachment were found by ultrasound biomicroscopy. Anti-glaucoma surgeries including trabeculotomy, trabeculectomy, non-penetrating deep sclerectomy, valve implantation and cyclocryotherapy were performed in 18 eyes. Eighty percent of the eyes which underwent trabeculectomy developed choroidal detachment after operation. Ten patients (11 eyes) were followed-up for 22 months on average. Intraocular pressure was significantly lower than that before the operation (t = 5.3956, P < 0.01). Intraocular pressure in all followed-up eyes was controlled at < or = 21 mm Hg (1 mm Hg = 0.133 kPa). CONCLUSIONS: The clinical features of Sturge-Weber syndrome-associated glaucoma include facial angiomas, open anterior chamber angle and choroidal hemangioma. Anti-glaucoma surgery can reduce the intraocular pressure effectively.

[Protection of autoimmunity induced by copolymer-1 on optic nerve: experiment with rat glaucoma models].

OBJECTIVE: To investigate whether copolymer-1 (Cop-1), a synthesized analogue of myelin basic protein, can protect the retina ganglion cells (RGCs) and possible mechanism thereof. METHODS: Vortex veins of rats were ligated to induce an increase of intraocular pressure (IOP) so as to establish glaucoma models. 106 rat models were randomly divided into 2 equal groups: Cop-1 Group undergoing subcutaneous injection of 200 microg Cop-1, and phosphate buffered solution (PBS) Group undergoing PBS injection as controls. Fluorogold was used to retrogradely label the RGCs. 10, 17, 24, and 31 days after the immunization some rats were killed with their eyeballs taken out. The fluorogold positive spots were calculated. Anti-rat T cell receptor (TCR) monoclonal antibody was used to mark T cells in the retina. RESULTS: 17, 24, and 31 days after the immunization, the RGC density of the Cop-1 Group were (2617 +/- 17)/mm(2), (2588 +/- 206)/mm(2), and (2394 +/- 15)/mm(2) respectively, all significantly higher than those of the PBS Group [(2357 +/- 37)/mm(2), (2277 +/- 340)/mm(2), and (2129 +/- 17)/mm(2) respectively, all P < 0.05]. 10, 17, 24, and 31 days after the immunization the numbers of T cells in the retina of Cop-1 Group were (11.3 +/- 2.8)/mm(2), (36.7 +/- 5.2)/mm(2), (33.9 +/- 3.0)/mm(2), and (21.4 +/- 5.9)/mm(2), all significantly higher than those of PBS Group (4.7 +/- 3.6)/mm(2), (19.7 +/- 2.4)/mm(2), (15.3 +/- 4.0)/mm(2), and (13.3 +/- 4.4)/mm(2) respectively, all P < 0.01). CONCLUSION: Cop-1 protects RGCs. The injury of RGCs induced by increased IOP results in congregation of T cells. Cop-1 increases the number of T-lymphocyte cells congregating in the retina, which may be related to its neuroprotection.

Mechanical Strain Induces Distinct Human Scleral Fibroblast Lineages: Differential Roles in Cell Proliferation, Apoptosis, Migration, and Differentiation.

Purpose: The purpose of this study was to explore the effect of mechanical strain on human scleral fibroblasts (HSFs) and compare cell behaviors of HSFs from distinct regions. Methods: Primary HSFs were cultivated using a digestive protocol. Cells were seeded on collagen I-coated Bioflex plates, and a FX-5000 tension system was used to perform biaxial mechanical strain in vitro. We applied 10%, 0.5-Hz mechanical strain. Cell behaviors of peripapillary and periphery HSFs were compared after the strain. Edu imaging, Cell Counting Kit-8 assay, and cell cycle flow cytometry were conducted to analyze cell proliferation ability. For cell apoptosis, flow cytometry of Annexin V/propidium iodide, caspase 3 activity, and Western blot were performed. Immunofluorescence, real-time PCR, and Western blot were used to investigate cell differentiation. A migration assay was also performed. Results: Under the mechanical strain of 10%, 0.5 Hz for 24 hours, the proliferation ability and cell apoptosis of peripapillary HSFs did not have a significant change. The expression of alpha-smooth muscle actin (α-SMA) slightly decreased. However, increased cell proliferation, attenuated cell apoptosis and more expression of α-SMA were shown in the periphery HSFs under the same condition. The migration rate was also increased for periphery HSFs, whereas it kept almost the same for peripapillary HSFs under 10%, 0.5-Hz strain for 8 hours. Conclusions: Mechanical strain affected the cell behaviors of HSFs. The different performance of cells from distinct regions may suggest familial linages of HSFs, probably induced by mechanical strain.

Lack of Association of rs1192415 in TGFBR3-CDC7 With Visual Field Progression: A Cohort Study in Chinese Open Angle Glaucoma Patients.

To investigate the association of known candidate genes with the visual field (VF) progression of primary open angle glaucoma (POAG) in a Han Chinese population. We included 440 POAG patients in this study. Fourteen previously reported single nucleotide polymorphisms (SNPs) at five different gene regions (TGFBR3-CDC7, TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) were genotyped. Age at diagnosis, gender, intraocular pressure (IOP), mean defect (MD) of VF, vertical cup disk ratio (VCDR), best corrected visual acuity (BCVA), central corneal thickness (CCT), and axial length (AL) were recorded at baseline. Patients were followed up for 5 years to evaluate VF progression over time. Clinical information and allele frequencies of 14 SNPs were compared between patients who progressed and who did not within 5 years by multivariate logistic regression. Survival analysis was performed to evaluate the contribution of the associated SNP by cox regression. Greater MD (P < 0.0001), increased VCDR (P = 0.0001), higher IOP (P = 0.0003), worse BCVA (P = 0.002), and older age (P = 0.030) at the baseline were associated with VF progression. Both multivariate logistic regression and cox regression survival analysis showed none of the 14 SNPs statistically associated with VF progression adjusted with age at diagnosis, gender, baseline MD, follow-up IOP, CCT, and AL. There were lack of association of SNPs at TGFBR3-CDC7, TMCO1, ATOH7, CDKN2B-AS1, SIX1/SIX6 loci with VF progression in POAG patients in Han Chinese. Further studies are needed to evaluate the association of genetic variants with VF progression.

Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucoma.

BACKGROUND AND OBJECTIVE: To measure the concentrations of transforming growth factor-betal and beta2 (TGF-beta1 and TGF-beta2) in the aqueous humor of patients with neovascular glaucoma (NVG). PATIENTS AND METHODS: Patients were divided into four groups: NVG secondary to central retinal vein occlusion (group 1), NVG secondary to proliferative diabetic retinopathy (group 2), central retinal vein occlusion without rubeosis (group 3), and senile cataract (group 4). The total TGF-beta 1 and TGF-beta2 concentrations in the aqueous humor of the four groups were measured by enzyme linked immunosorbent assay. RESULTS: The mean concentrations of total TGF-betal were 600.7 +/-436.7 microg/mL in group 1, 802.0 +/-359.5 pg/mL in group 2, and undetectable in groups 3 and group 4 (P < .05). The mean concentrations of total TGF-beta2 were 6,307.9+/- 2,206.2 microg/mL in group 1, 5,908.0+/-2,033.2 microg/mL in group 2, 899.7+/- 425.6 microg/mL in group 3, and 385.7 +/-89.9 microg/mL in group 4. The total TGF-betal and TGF-beta2 concentrations in groups 1 and 2 were significantly higher than those in groups 3 and 4, whereas the total TGF-beta2 concentration in group 3 was significantly higher than that in group 4 (P < .05). There was no significant difference in the TGF-betal or TGF-beta2 concentrations between groups 1 and 2 (P> .05). CONCLUSIONS: The abnormally high concentrations of TGF-betal and TGF-beta2 in the aqueous humor of patients with NVG may explain some aspects of the pathogenesis of NVG and the high failure rate of filtering operations in NVG.

[Selective laser trabeculoplasty in the treatment of primary open-angle glaucoma].

OBJECTIVE: To investigate the efficacy and safety of selective laser trabeculoplasty (SLT) in the treatment of primary open angle glaucoma (POAG). METHODS: In a prospective non-randomized clinical study, 63 patients (85 eyes) with POAG and medically uncontrolled intraocular pressure (IOP) underwent SLT. A total of 50 +/- 5 adjacent but nonoverlapping spots were placed over inferior 180 degrees of the trabecular meshwork using a 532 nm, Q-switched, Nd: YAG laser at energy levels ranging from 0.6 - 1.8 mJ per pulse. After SLT, the eyes continued to receive the identical drug regimen. All patients were observed before and 1, 2 hours, 1, 7 and 14 days, and 1, 2, 3, 6, 9, 12, 18, and 24 months after the treatment. RESULTS: The average pre-operative IOP was (25 +/- 4) mm Hg (1 mm Hg = 0.133 kPa). The mean IOP reduction from baseline were 8.1 mm Hg (32.0%) 1 day after the SLT, 5.6 mm Hg (22.1%) 7 days after the SLT, 4.7 mm Hg (18.6%) 14 days after the SLT, 5.5 mm Hg (21.7%) 1 month after the SLT, 5.1 mm Hg (20.2%) 2 months after the SLT, 5.9 mm Hg (23.3%) 3 months after the SLT, 5.2 mm Hg (20.6%) 6 months after the SLT, 4.0 mm Hg (15.8%) 9 months after the SLT, 4.2 mm Hg (16.6%) 12 months after the SLT, 3.8 mm Hg (15.0%) 18 months after the SLT, and 3.3 mm Hg (13.0%) 24 months after the SLT (P < 0.01 or 0.05). Adverse reactions were minimal, including conjunctival injection, mild anterior chamber reaction, and transient pressure spike. CONCLUSION: SLT is a safe, and effective method of reducing IOP in POAG patients.

A Gelated Colloidal Crystal Attached Lens for Noninvasive Continuous Monitoring of Tear Glucose.

Patients of diabetes mellitus urgently need noninvasive and continuous glucose monitoring in daily point-of-care. As the tear glucose concentration has a positive correlation with that in blood, the hydrogel colloidal crystal integrated into contact lens possesses promising potential for noninvasive monitoring of glucose in tears. This paper presents a new glucose-responsive sensor, which consists a crystalline colloidal array (CCA) embedded in hydrogel matrix, attached onto a rigid gas permeable (RGP) contact lens. This novel sensing lens is able to selectively diffract visible light, whose wavelength shifts between 567 and 468 nm according to the alternation of the glucose concentration between 0 and 50 mM and its visible color change between reddish yellow, green, and blue. The detection limit of responsive glucose concentration can be reduced to 0.05 mM. Its combination with a contact lens endows it with excellent biocompatibility and portability, which shows great possibility for it to push the development of glucose-detecting devices into new era.