The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

Prevalence, ethnic differences and risk factors of primary angle-closure glaucoma in a multiethnic Chinese adult population: the Yunnan Minority Eye Study.

PURPOSE: To describe the prevalence and risk factors of primary angle-closure glaucoma (PACG) and to explore nationality difference in Chinese. METHODS: The Yunnan Minority Eye Study was conducted in a rural multiethnic area in Yunnan province and included 6546 participants aged over 50 years. PACG was diagnosed based on International Society of Geographical and Epidemiologic Ophthalmology criteria by experienced ophthalmologists. Multivariate regression modelling was conducted to examine risk factors for PACG. Principal component analyis (PCA) was performed to evaluate the effects of ethnicity on PACG. RESULTS: The overall prevalence of PACG was 0.7% (95% CIs: 0.5% to 0.9%). PCA indicated that ethnicity is significantly related to the presence of PACG (p<0.001) after controlling for other risk factors. In addition, higher PACG prevalence was also correlated with older age (60-69 years group (OR: 3.47; 95% CI: 1.11 to 10.84; p<0.05) and 70-79 years group (OR: 4.71; 95% CI: 1.40 to 15.86; p<0.05) as compared with 50-59 years group), higher intraocular pressures (OR: 1.26; 95% CI: 1.17 to 1.36; p<0.001), shorter axial lengths (OR: 0.42; 95% CI: 0.32 to 0.56; p<0.001) and thinner central corneal thicknesses (OR: 0.89; 95% CI: 0.81 to 0.99; p<0.05). CONCLUSIONS: This multiethnic study on Chinese adults living in the same geographical location indicated that ethnicity is a significant risk factor for PACG. However, there were still some of the effects of ethnic differences on the prevalence of PACG that could not be explained and further studies should take culture and lifestyle factors into account.

Peripapillary vessel density correlates with visual field mean sensitivity in highly myopic eyes.

PURPOSE: To identify the global and regional distribution of peripapillary vessel density (pVD) and try to find out the relationships between pVD and the visual field mean sensitivity (VFMS) in healthy myopic eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred and twenty-two participants (393 eyes) with myopia (myopic refractive error < - 0.5 diopters) from two clinical centers were recruited in this study and were divided into 4 groups according to the spherical equivalent (SE): Group1:- 0.5D ≥ SE > - 6.00D, Group2: - 6.00D ≥ SE > - 8.00D, Group3:- 8.00D ≥ SE > - 10.00D, Group4:SE ≤ -10.00D.The pVD assessed with optical coherence tomography angiography (OCTA) was quantified in 8 sectors. Peripapillary retinal nerve fibre layer (pRNFL) imaging was performed with SD-OCT. Visual field (VF) tests were performed with the 30-2 SITA standard program on the Humphrey 750i Visual Field Analyzer and were grouped into 8 regions that matched the structure. RESULTS: The pRNFL had no significant difference in all groups (p = 0.422). The average pVD were significantly lower in group 4 (47.61 ± 6.58) than in group 2 and 3 (51.49 ± 3.21, 50.48 ± 3.43 respectively) (p < 0.05). While both pVD in group2 and 3 were statistically lower than group1 (52.77 ± 2.86). The average VFMS was significantly lower in group 4 (901.85 ± 386.54) than other three groups (1169.15 ± 328.94, 1081.77 ± 338.83, 1076.89 ± 358.18, for group1,2,3 respectively). The pVD and VFMS were positively correlated in group3 (r = 0.184) and group4 (r = 0.476) (p < 0.05). Linear regression analysis demonstrated that VFMS were positively associated with pVD especially in temporal and nasal quadrants in myopic eyes. CONCLUSIONS: The pVD shows a significant positive correlation with VFMS in highly myopic eyes with SE ≤ - 8.00D. We suggest that pVD measurement by OCTA could be a sensitive and useful method for monitoring myopic functional change.

Knowledge of glaucoma and associated factors among primary glaucoma patients in Kunming, China.

BACKGROUND: To investigate the level of knowledge, attitude, and practices about glaucoma and associated factors among primary glaucoma patients in Kunming, China. METHODS: A hospital-based study was conducted on 93 patients from the First Affiliated Hospital of Kunming Medical University. Interviewer-administered questionnaires were used to collect data after written informed consent. Data were analyzed by SPSS 19.0. Univariate and multivariate logistic regression models were used to identify factors. A Chi-square test was used to analyze the association between knowledge of glaucoma and medication compliance, Mann-Whitney U test was performed to assess the relationship between knowledge of glaucoma and quality of life in patients with glaucoma. P-value < 0.05 was considered statistically significant. RESULTS: Among 93 patients, 55 (59.14%) were aware of glaucoma, 48 (51.61%) had good knowledge of glaucoma, while 45 (48.39%) had poor knowledge. Younger age and duration of glaucoma were associated positively with knowledge of glaucoma. 87 (93.54%) patients got knowledge of their disease from doctors. 79.17% of respondents could use all the anti-glaucoma medications on time, out of which 54.17% had good knowledge of glaucoma while 25.00% had poor knowledge of glaucoma. 30.56% of respondents used to stop anti-glaucoma medications on their own out of which only 9.72% had good knowledge of glaucoma while 20.83% had poor knowledge of glaucoma. Patients with good knowledge of glaucoma had lower scores on the Glaucoma Quality of Life-15 questionnaire. Thus, the compliance to anti-glaucoma medications and glaucoma-related quality of life were better in patients with good knowledge. CONCLUSIONS: The level of knowledge of glaucoma among patients in Kunming is relatively low. Improving knowledge with suitable content for patients through effective multiple means such as the mass media rather than relying only on ophthalmologists may be a veritable first step in combating blindness from glaucoma and enhancing patients' quality of life.

Evaluation of Macular and Retinal Ganglion Cell Count Estimates for Detecting and Staging Glaucoma.

Purpose: To investigate the clinical significance of macular estimated retinal ganglion cell (mRGC) and estimated retinal ganglion cell (eRGC) in the diagnosis and staging of glaucoma. Methods: This is a cross-section study. All enrolled subjects underwent standard automated perimetry (SAP) and optical coherence tomography (OCT) examination. Swedish Interactive Threshold Algorithm (SITA)-FAST detection strategy and 24-2, 10-2 detection programs were employed in SAP assessment. The visual-field parameters and OCT parameters were calculated according to three formulas to obtain the eRGC and mRGC1 or mRGC2. The efficiency of eRGC, mRGC1, and mRGC2 estimates for the staging of glaucoma was compared. The sensitivity and specificity of each parameter for diagnosis of glaucoma were analyzed using the receiver operating characteristic (ROC) curve. Results: A total of 119 eyes were included in the analysis. Compared with the healthy controls, eRGC, mRGC1, and mRGC2 estimates were significantly decreased in patients with glaucoma. As glaucoma progressed, eRGC, mRGC1, and mRGC2 estimates were gradually reduced. In preperimetric glaucoma, mRGC1, mRGC2, and eRGC were reduced by 13.2, 14.5, and 18%, respectively. In the mild stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 28, 34, and 38%, respectively. In the advanced stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 81, 85, and 92% respectively. The proportion of retinal ganglion cell (RGC) loss in the macula was close to that outside the macula. The specificity at 95% gave a sensitivity of 95.51, 86.52, and 87.64% for eRGC, mRGC1, and mRGC2, respectively. The sensitivity of structural parameters macular ganglion cell complex thickness and retinal nerve fiber layer (RNFL) were 98.88 and 95.51%, respectively. The sensitivity of functional parameters mean deviation (24-2) and visual field index (VFI) were 80.90 and 73.03%, respectively. The area under ROC curve of mRGC1, mRGC2, and eRGC were 0.982, 0.972, and 0.995 (P < 0.0001), respectively. Conclusion: Estimated retinal ganglion cell, mRGC1, and mRGC2 provide value to the staging of glaucoma and better diagnostic performance. Macular RGC estimatesthat integration of both structural and functional damages in macular may serve as a sensitive indicator for assessing macular damage in glaucoma and are of importance for the diagnosis and progression management of glaucoma.

Comparison of the SITA Faster-a new visual field strategy with SITA Fast strategy.

AIM: To compare visual field defects using the Swedish Interactive Thresholding Algorithm (SITA) Fast strategy with SITA Faster strategy, a newly developed time-saving threshold visual field strategy. METHODS: Ninety-three participants (60 glaucoma patients and 33 normal controls) were enrolled. One eye from each participant was selected randomly for the study. SITA Fast and SITA Faster were performed using the 24-2 default mode for each test. The differences of visual field defects between the two strategies were compared using the test duration, false-positive response errors, mean deviation (MD), visual field index (VFI) and the numbers of depressed test points at the significant levels of P<5%, <2%, <1%, and <0.5% in probability plots. The correlation between strategies was analyzed. The agreement between strategies was acquired by Bland-Altman analysis. RESULTS: Mean test durations were 246.0±60.9s for SITA Fast, and 156.3±46.3s for SITA Faster (P<0.001). The test duration of SITA Faster was 36.5% shorter than SITA Fast. The MD, VFI and numbers of depressed points at P<5%, <2%, <1%, and <0.5% in probability plots showed no statistically significant difference between two strategies (P>0.05). Correlation analysis showed a high correlation for MD (r=0.986, P<0.001) and VFI (r=0.986, P<0.001) between the two strategies. Bland-Altman analysis showed great agreement between the two strategies. CONCLUSION: SITA Faster, which saves considerable test time, has a great test quality comparing to SITA Fast, but may be not directly interchangeable.

Effects of miRNA-140 on the Growth and Clinical Prognosis of SMMC-7721 Hepatocellular Carcinoma Cell Line.

BACKGROUND: A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. METHODS: The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. RESULTS: QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues (P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion (P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion (P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times (P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS (P = 0.004) and OS times (P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

Impact of binocular integrated visual field defects on healthy related quality of life in glaucoma.

ABSTRACT: To investigate the impact of different types of binocular integrated visual field defects on the quality of life in glaucoma.Ninety-six patients with primary glaucoma were divided into 5 groups with 25, 24, 11, 15, and 21 patients according to types of the binocular integrated visual field (BVF) defects. The criteria for BVF grouping included mild visual field defect in binocular eyes, mild visual field defect in 1 eye and moderate or advanced defect in the other, moderate and non-overlapping visual field defect in both eyes, overlapping and moderate visual field defect in binocular eyes, and severe defect in both eyes, respectively. The visual field (VF) evaluation was based on H-P-A visual field grading system. Visual acuity, visual field tests and Glaucoma Quality of Life-15 Questionnaire (GQL-15) were performed for enrolled patients, and binocular visual field results were integrated. The changes and correlations of the Visual field index values and quality of life scores were compared among the 5 groups. The main factors affecting the quality of life in glaucoma were analyzed by multiple regression analysis.The best binocular integrated visual field index (BVFI) and optimal quality of life were observed in group A. The BVFI of group B was better than that of group C or group D, but the peripheral vision glare and dark adaptation were worse. No significant difference was noted between group C and group D in terms of BVFI. However, the glare and dark adaptation in group C were better than that in group D. The BVFI was the lowest and the quality of life was the worst in group E. In all, BVFI and decibels (dB) values were negatively correlated with GQL-15 scores and positively correlated with patients' quality of life.Binocular integrated visual field accurately reflects the visual function in glaucoma. Higher binocular integrated visual field indices represent a better quality of life for patients with glaucoma. Mild to moderate synchronous or complementary binocular VF defects had a slight effect on the quality of life, while severe and non-compensated VF loss significantly impacts on quality of life in glaucoma patients.

Ethnic variation in prevalence, self-reported barriers and outcome of cataract surgery in a rural population in southwestern China: the Yunnan minority eye study.

BACKGROUND: As a part of the Yunnan Minority Eye Studies, the purpose of this study was to determine the prevalence, barriers and visual acuity outcomes of cataract surgery in a multiethnic adult population in rural areas of southwestern China. METHODS: A population-based cross-sectional survey was conducted with participants of Bai, Yi, and Han ethnicity aged ≥50 years in Yunnan. A detailed eye examination was performed. Information on the date, setting, type, and complications of cataract surgery were recorded in the examination of cataract-operated eyes. RESULTS: Of 6546 subjects (2133 Bai ethnicity, 2208 Yi ethnicity and 2205 Han ethnicity), the prevalence of cataract surgery was 6.0%, with 4.6% in Bai, 7.0% in Yi, and 6.4% in Han ethnicity. Cataract Surgical coverage (CSC) among those with presenting visual acuity (PVA) < 20/200 in both eyes because of cataract was 53.3%, with 52.8% in Bai, 64.4% in Yi, and 45.3% in Han ethnicity. CSC was associated with Yi ethnicity, younger age, and higher education level, while unoperated cataract was associated with Han ethnicity, older age, and illiterate. The main barrier to cataract surgery was lack of awareness and knowledge, cost, and fear. Among the 525 cataract-operated eyes, PVA and best-corrected visual acuity (BCVA) of 20/63 or better was 44.5 and 67.2%, respectively, with 48.1 and 65.9% in Bai, 47.8 and 75.4% in Yi, 39.1 and 59.9% in Han ethnicity. Han ethnicity, aphakia, earlier year of surgery, lower-level surgical hospital and illiterate were associated with postoperative visual impairment defined by PVA, while Han ethnicity, aphakia, and illiterate were associated with that defined by BCVA. The principal causes of postoperative visual impairment were retinal disorders (26.8%), posterior capsule opacification (25.1%), refractive error(22.7%), and glaucoma (9.3%). CONCLUSIONS: Han ethnicity had a lower CSC and relatively poor visual outcomes compared with ethnic minorities. Further effective effort to remove barriers and provide sight restoration is warranted.

Effect of intraocular lens implantation on visual field in glaucoma and comorbid cataracts.

AIM: To investigate the effects of intraocular lens (IOL) implantation on visual field (VF) in patients with glaucoma and comorbid cataracts (G&C) with different disease severities. METHODS: Totally 56 eyes of 50 patients with primary G&C were included. All patients were divided into three groups based on the severity of the VF defect: the mild, moderate, and severe stage. Phacoemulsification was performed for cataract removal combined with IOL implantation. Visual acuity (VA) and VF tests were performed for all enrolled patients, up to 3mo after surgery. Changes in VF threshold and global VF index in various groups were also recorded before and after surgery. The mean light sensitivity (MS) values and the changes following surgery (DMS) were compared between the three groups. Advanced Glaucoma Intervention Study (AGIS) scoring was analyzed on all VF results for analysis of changes in VF before and after surgery. RESULTS: Following surgery, the MS values of the three groups of G&C increased significantly, while the AGIS scores decreased statistically in all groups. The DMS values for the three zones in moderate and severe stage but not mild stage were statistically different between zones. The DMS value was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.05). The DMS was significantly higher in zone I than that in zone III in moderate stage patients (zone I>zone II>zone III; P<0.01), while the DMS values in the severe stage patients was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.01). CONCLUSION: The mean VF sensitivity of glaucoma patients increased significantly after cataract removal and IOL implantation. Variations in the severity and distribution of characteristics of VF defects result in differences in postoperative VF improvements after cataract surgery. The magnitude of increase in VF sensitivity is associated with VF defect characteristic in glaucoma.

The in vitro anti-fibrotic effect of Pirfenidone on human pterygium fibroblasts is associated with down-regulation of autocrine TGF-ß and MMP-1.

We aimed to investigate the in vitro effect of pirfenidone (PFD) on proliferation, migration and collagen contraction of human pterygium fibroblasts (HPFs). HPFs were obtained from tissue explants during pterygium surgery. After treatment with pirfenidone, the HPFs proliferation was measured by MTT, cell cycle progression measured by flow cytometry, cell migration measured by the scratch assay, and cell contractility evaluated in fibroblast-populated collagen gels. The expression of TGF-ß1, TGF-ß2, MMP-1 and TIMP-1 were also determined with quantitative PCR, western blot and immunofluorescence staining. Results showed pirfenidone markedly inhibited HPFs proliferation with an IC50 of approximately 0.2 mg/ml. After treatment with 0.2 mg/ml pirfenidone for 24 hours, HPFs were at G0/G1 cell cycle arrest, with significantly reduced cell migration capability and collagen contraction, decreased mRNA and protein expressions of TGF-ß1, TGF-ß2 and MMP-1, and no alterations of TIMP-1 expression. Thus, we have concluded that pirfenidone at 0.2 mg/ml inhibits proliferation, migration, and collagen contraction of HPFs, which is associated with decreased expression of TGF-ß and MMP-1, and pirfenidone might represent a potentially therapeutic agent to prevent the recurrence of pterygium after surgery.

Upregulation of Long Non-Coding RNA ENST00000429227.1 Is Correlated with Poor Prognosis in Human Hepatocellular Carcinoma.

BACKGROUND Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory role in many tumors. This study was designed to investigate the expression of lncRNA ENST00000429227.1 in hepatocellular carcinoma (HCC) and to determine whether the expression of lncRNA ENST00000429227.1 affects the prognosis of HCC. MATERIAL AND METHODS lncRNA ENST00000429227.1 showing differences in expression between M1 and M2 was screened by microarray expression measurements. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA ENST00000429227.1 in 161 HCC patients. The chi-square test was used to evaluate the relationship between the expression of ENST00000429227.1 and clinicopathological parameters. A survival curve was drawn and analyzed by Kaplan-Meier method. Cox regression was used for univariate and multivariate analysis to determine whether lncRNA ENST00000429227.1 is an independent factor of the occurrence and prognosis of HCC. RESULTS A total of 3703 differentially expressed lncRNAs were obtained, of which 1777 were upregulated and 1926 were downregulated, with multiple change >1.5. The expression of lncRNA ENST00000429227.1 was upregulated in M2 cells. The expression of lncRNA ENST00000429227.1 in HCC tissues was higher than that in adjacent normal tissues (p<0.05), which was correlated with pathological parameters such as surgical margin (p=0.042), AFP (p=0.022) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.008). Survival analysis showed that high expression of lncRNA ENST00000429227.1 was associated with a decrease in overall survival (OS) rate of HCC patients. Cox regression analysis showed that high expression of ENST00000429227.1 may be an independent risk factor affecting the prognosis of HCC patients. CONCLUSIONS The results suggest that upregulation of ENST00000429227.1 is associated with poor prognosis of HCC patients, and may be a new biomarker for the diagnosis of HCC.

Pirfenidone suppresses the abnormal activation of human Müller cells after platelet-derived growth factor-BB stimulation.

AIM: To determine the effect of pirfenidone on the activated human Müller cells by platelet-derived growth factor-BB (PDGF-BB). METHODS: The primary human Müller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Müller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor (TGF)-ß1, -ß2, and pigment epithelium-derived factor (PEDF) was estimated with real-time polymerase chain reaction (PCR), Western blot and immunofluorescence analyses. RESULTS: A pathogenic/proliferative model of Müller cells was established by stimulating normal cultured Müller cells with 10 ng/mL PDGF-BB for 48h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-ß1 and TGF-ß2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. CONCLUSION: Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Müller cells stimulated with PDGF-BB through down-regulation of TGF-ß1/TGF-ß2 and up-regulation of PEDF.

Prevalence, types and awareness of glaucoma in a multi-ethnic population in rural China: the Yunnan Minority Eye Study.

PURPOSE: To determine the prevalence, types and awareness of glaucoma in a rural community in China and to examine possible ethnic variations. METHODS: The Yunnan Minority Eye Study was a multi-ethnic community-based eye survey using random cluster sampling strategies. 2133 Bai, 2205 Han and 2208 Yi Chinese aged 50 years or older participated in this study. Glaucoma including primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG) and secondary glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. RESULTS: The overall age-standardized prevalence of all glaucoma was 2.6% (95% confidence interval [CI]: 2.2-3.1%) in this population. It was 1.8% (95% CI: 1.1-1.9%) for POAG and 0.5% (95% CI: 0.9-1.6%) for PACG, respectively. Among 29 people with secondary glaucoma, 27 (93%) were blind in at least one eye. The presence of primary open-angle glaucoma was associated with male gender (odds ratio [OR] = 2.94; comparing men with women), Yi ethnicity (OR = 2.27; comparing Yi with Han people), higher IOP (OR = 1.09 per mmHg increase), and the presence of myopia (OR = 1.84). Of the 212 participants with glaucoma, only 38 (18%) were aware of the disease and had been diagnosed previously as having glaucoma or suspected glaucoma. Patients who were better educated tended to be aware of the disease. CONCLUSIONS: Significant ethnic difference in the prevalence of POAG was observed in this study. The low awareness of glaucoma highlights the pressing need to increase public awareness of this potentially blinding condition in rural China.

Activation of γ-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats.

BACKGROUND: Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study. METHODS: According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial librillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory. RESULTS: The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups. CONCLUSIONS: Activation of GABAA R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.

Activation of γ-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study.</p><p><b>METHODS</b>According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial librillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory.</p><p><b>RESULTS</b>The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups.</p><p><b>CONCLUSIONS</b>Activation of GABAA R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.</p>