Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma.

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- ß signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

Glaucoma Characteristics and Influencing Factors during the COVID-19 Pandemic in the Huizhou Region.

Objective: Glaucoma in individuals who tested positive for the coronavirus disease 2019 (COVID-19) during the pandemic outbreak has not been comprehensively studied. Therefore, this study aimed to analyze the characteristics and risk factors of glaucoma during the COVID-19 pandemic in Huizhou. Methods: Retrospective data from outpatients with glaucoma at the Huizhou Hospital Affiliated with Guangzhou Medical University and Longmen County People's Hospital were collected during two periods: the COVID-19 pandemic period (Phase A: December 1, 2022, to January 19, 2023) and the prevention and control period (Phase B: December 1, 2021, to January 19, 2022). The demographic characteristics of the outpatients during both phases were compared. The characteristics of glaucoma in patients with COVID-19 during Phase A were examined. Multivariate logistic regression analysis was used to identify factors influencing the development of acute angle-closure glaucoma (AACG) in Phase A patients. Results: The proportion of patients with glaucoma was significantly higher during Phase A than during Phase B at both hospitals. No statistically significant differences were observed between patients with glaucoma during Phases A and B for age, sex, and region. A high COVID-19-positive rate was associated with old age, females, AACG, newly diagnosed glaucoma, and binocular involvement during phase A. Females testing positive for COVID-19, glaucoma that started after testing positive for COVID-19, and a history of medication use were associated with a higher proportion of AACG in phase A. Multivariable logistic regression analysis identified testing positive for COVID-19 as an independent potential risk factor for developing AACG. Conclusion: In summary, during the COVID-19 pandemic in Huizhou, patients with COVID-19 were primarily affected by AACG, especially females, older individuals, and those with binocular involvement. Testing positive for COVID-19 increases the risk of developing AACG.

Effects of chronic elevated intraocular pressure on parameters of optical coherence tomography in rhesus monkeys.

AIM: To determine the progression of parameters from optical coherence tomography (OCT) in chronic elevated intraocular pressure (IOP) monkeys. METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer (RNFL) thickness, and parameters from optic nerve head (ONH) analysis were collected before and after laser treatments biweekly for up to 28wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model. RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2wk after elevated IOP induction (P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk. CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.

Elevated Intraocular Pressure Induces Amyloid-ß Deposition and Tauopathy in the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma.

Purpose: Recent evidence has suggested a potential association between Alzheimer's disease (AD) and glaucoma and found significant deposition of amyloid-ß (Aß) and Tau protein in the retinas of glaucoma patients. However, no coherent finding has emerged regarding the AD-like changes in the central visual system (CVS). Studies confirming the presence of Aß and Tau neuropathology are warranted to identify the underlying mechanism that contributes to the visual impairment observed in glaucoma. Methods: A chronic glaucoma model was established in rhesus monkeys. The retina, optic nerve, CVS including the lateral geniculate nucleus (LGN) and primary visual cortex (V1), and cognitive areas including the hippocampus (Hpp) were evaluated. Aß 1-42 and phosphorylated-Tau (p-Tau) were tested in the aforementioned structure using immunohistochemistry, Western blotting and ELISA, and the neuritic plaques and argyrophilic structures/neurofilaments were observed using silver staining and transmission electron microscopy (TEM). Results: Immunohistochemistry revealed positive Aß and p-Tau labeling in the LGN. According to Western blotting assay and ELISA, Aß and p-Tau were present in the LGN. Aß also was expressed weakly in the primary visual cortex. In contrast, the hippocampus, which is the most severely affected region in AD, showed no positive labeling. Structurally, silver staining and TEM revealed neuritic plaques and argyrophilic structures/neurofibrillary tangles, in the LGN. Conclusions: For the first time to our knowledge, these data collectively establish the existence of hallmark AD-like pathologies in the glaucomatous LGN. Our results may provide new targets for developing research therapies that will enhance neuroprotection in glaucoma patients.

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population.

BACKGROUND: To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma. METHOD: In total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis. PRINCIPLE FINDINGS: The average follow-up time was 12.7±5.8 months (mean±SD). We observed a significant reduction in the mean IOP from 39.9±12.6 mm Hg before surgery to 19.3±9.6 mm Hg at the final follow-up. The complete success rate was 59.5%, and the qualified success rate was 83.5%. The number of previous surgeries was negatively correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99). Patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control IOP (P<0.01). The primary complication was determined to be a flat anterior chamber (AC). CONCLUSION: AGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP.

Analysis of a method for establishing a model with more stable chronic glaucoma in rhesus monkeys.

In this study, we utilized yellow-wavelength laser treatment and measured aqueous outflow facility to establish a model for chronic glaucoma in rhesus monkeys. We then compared the effects of photocoagulation resulting from exposure to the yellow laser or to a green laser. Twelve rhesus monkeys were used to establish the model, and the yellow and green lasers were utilized for 360° photocoagulation in the anterior-chamber angles of the right eye in all subjects. After certain periods of time before and after the creation of the glaucoma model, the cornea, aqueous humor, optic cup, intraocular pressure (IOP), outflow facility, retinal nerve fiber layer (RNFL), and pathology of the trabecular meshwork were analyzed. Both the yellow and green lasers caused an increase in IOP compared with before photocoagulation (18.6 ± 2.6 mm Hg and 16.1 ± 1.8 mm Hg, respectively), with an average photocoagulation from the yellow and green lasers of 39.2 ± 7.9 mm Hg and 30.3 ± 4.7 mm Hg, respectively (P < 0.01). However, the success rate of a second photocoagulation treatment in the yellow laser group was significantly higher than in the green laser group (P < 0.05). After the increase in IOP, both groups exhibited an inflammatory response in the anterior segment, enlarged cupping, and a decrease in the average thickness of the RNFL. However, the yellow laser caused less corneal edema than the green laser (P < 0.05), and the outflow facility of the two groups (0.33 ± 0.09 and 0.30 ± 0.07 µl/min/mm Hg for the yellow and green lasers, respectively) showed different degrees of differences (0.05 ± 0.02 and 0.07 ± 0.02 µl/min/mm Hg for the yellow and green lasers, respectively) into the abnormal range after photocoagulation. Pathological examination revealed that the depth of destruction of the trabecular meshwork appeared to be deeper in the yellow laser group than in the green laser group. In conclusion, application of a yellow laser combined with measuring aqueous outflow facility produced a glaucoma model with a minor inflammatory response and few IOP fluctuations.

Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model.

Primary open angle glaucoma (POAG) is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs). In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi) and late or degraded autophagic vacuoles (AVd) accumulated in the ganglion cell layer (GCL) and in the inner plexiform layer (IPL) as determined by transmission electron microscopy (TEM) analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1) and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.