This study aims to report the most up-to-date information about the global disease burden of glaucoma from 1990 to 2019 and to forecast trends in the next few years. Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The prevalence and disability-adjusted life years (DALYs) of glaucoma from 1990 to 2019 were reported. Finally, trends in the years following 2019 were predicted by Bayesian age–period–cohort (BAPC) models. We showed that, globally, the number of prevalent cases was 3,881,624 [95% uncertainty interval (UI): 3,301,963 to 4,535,045] in 1990 and increased to 7,473,400 (95% UI: 6,347,183 to 8,769,520) in 2019, while the age-standardized prevalence rate decreased from 111.92 [95% uncertainty interval (UI): 94.76 to 130.28 per 100,000] in 1990 to 94.68 (95% UI: 80.42 to 110.87 per 100,000) in 2019. The DALY number of glaucoma increased between 1990 and 2019, from 442,182 (95% UI: 301,827 to 626,486) in 1990 to 748,308 (95% UI: 515,636 to 1,044,667) in 2019. There was a significantly negative association between the sociodemographic index (SDI) and age-standardized DALY rates. The BAPC showed that the age-standardized DALY rate is predicted to decrease gradually in both males and females over the next few years. In summary, from 1990 to 2019, the global burden of glaucoma increased and the age-standardized DALY rate is predicted to decrease in the next few years. With the largest burden of glaucoma found in low-SDI regions, clinical diagnosis and treatment in such areas are more challenging and may warrant more attention.

Metformin has effective therapeutic effects in anti-tumor and anti-fibrotic diseases. However, how the antifibrotic effect of metformin in the eye and how it is transferred are still unclear. Here, the eye drop of metformin treatment was studied in Sprague–Dawley (SD) rats of glaucoma filtrating surgery (GFS). Rats were administered randomly bilateral drops: control group (without surgery), GFS group, metformin group or mitomycin C (MMC) group (sponge application intraoperatively, 0.02%). Bleb features and intraocular pressure (IOP) were assessed for postoperative week 4. Metformin effectively inhibited fibrosis and improved the surgical outcomes of GFS. In vitro, we found that the degree of oxidative stress and fibrosis in metformin pretreated-Human Conjunctival Fibroblasts (HConFs) were reduced; the pro-fibrotic response of HConFs were decreased by inducing macrophagic polarity changes. Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin. Together, this experiment indicates that metformin enters into HConFs cell with OCTs, which can protect against filtrating blebs scar formation in SD rats of GFS via activating AMPK/Nrf2 axis and the downregulation of profibrogenic and inflammatory biomarkers.

The correlation between obesity and primary open-angle glaucoma (POAG) has not yet been fully established. The aim of this study was to investigate the causal relationship between obesity and POAG by a two-sample Mendelian randomization (MR) study. In this study, body mass index (BMI), an index to evaluate general obesity, and waist and hip circumference, indices to evaluate abdominal obesity, were selected as exposures in MR analysis. Single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). Summary data from genome-wide association studies (GWASs) based on a European ancestry by Locke et al., with regard to BMI, and Shungin et al., with regard to waist and hip circumference, were used. Genetic predictors of POAG were obtained from public GWAS summary data. To assess the causal effect of obesity on POAG, the inverse variance-weighted (IVW) method was used as the primary method, and other methods, such as MR–Egger, weighted median, simple mode, and weighted mode, were also used as complementary analyses. Finally, we performed Cochran’s Q statistic to assess heterogeneity, and sensitivity analysis was performed to evaluate the reliability and stability of the MR results. MR analysis showed that BMI has a positive effect on the risk of POAG, with 1 standard deviation (SD) increase in BMI; the risk of POAG increases by approximately 90.9% [OR = 1.909; 95% CI= (1.225, 2.975); p = 0.0042)] (analyzed by IVW); there were no heterogeneity and pleiotropy in the result; and waist circumference also had a positive effect on the risk of POAG [OR = 2.319; 95% CI= (1.071, 5.018); p = 0.033)] analyzed by weighted median. As hip circumference increases, with 1 SD increase in hip circumference, the risk of POAG increases by approximately 119% [OR = 2.199; 95% CI= (1.306, 3.703); p = 0.00305)] estimated by IVW, there were not heterogeneity and pleiotropy as for the result. Our study for the first time confirms that obesity might increase the risk of POAG using two-sample MR analysis. These results might provide guidance on the prevention and treatment of POAG.

AIM: To confirm whether exosome-mediated delivery of aptamer S58 (Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts (HConFs) and a rat glaucoma filtration surgery (GFS) model. METHODS: To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293T cells by PEI transfection to determine the effect of Exo-S58 in HConFs and a rat GFS model. RESULTS: Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HConFs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats. CONCLUSION: The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HConFs cells and rat GFS models.

Excessive scarring is the main cause of surgical failure in glaucoma filtration surgery. S58 has been shown to have an excellent antifibrotic effect but its duration of action is not sufficient to achieve the desired antiscarring effect. In this study, a light-cured bioadhesive hydrogel composed of GelMA and oxidized dextran (ODex), namely, GelDex, was used to load S58 (GelDex-S58). The microscopic morphology of GelDex-S58 appeared to be a porous structure with good slow-release properties and suitable degradation time. Cell Counting Kit-8, cell scratch and transwell assays showed that GelDex-S58 significantly reduced TGF-β-induced fibroblast proliferation, increased migration and invasion ability. In in vivo studies, GelDex-S58 treatment prolonged follicular retention, reduced mean intraocular pressure, and significantly reduced collagen deposition and α-SMA expression levels in the conjunctival tissue compared to treatment with S58 alone. In conclusion, GelDex-S58 could reduce scar formation after glaucoma filtration surgery.

Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.