This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism. In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEV^{miR-22-3p (-)} on AGEs-induced microglia was compromised as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV. These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.

Oxidative stress and inflammation induced by reactive oxygen species (ROS) play important roles in the development of diabetic retinopathy (DR). Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which is negatively controlled by Cullin3-RING E3 ligase (CRL3) and controls ROS levels, is compromised in DR. CRL3 activity is regulated by Cullin3 neddylation. Nonetheless, the relationship between Cullin3 neddylation and DR remains uncertain. The goal of this study was to evaluate the effect of Cullin3 neddylation on DR and its underlying mechanisms by utilizing MLN4924, a neddylation inhibitor. Cullin3 neddylation was elevated in diabetic rats’ retinas as well as in advanced glycation end products (AGEs)-induced endothelial cells. Inhibiting neddylation of Cullin3 with MLN4924 downregulated Nrf2 ubiquitination, promoted Nrf2 accumulation, suppressed ROS-induced oxidative stress and inflammation, and attenuated blood-retinal barrier (BRB) breakdown in both diabetic vivo and vitro models. However, the beneficial impact of MLN4924 was compromised when Nrf2 was suppressed with siRNA in vitro. This study showed that inhibition of Cullin3 neddylation with MLN4924 exerted protective effect on DR by activating Nrf2 signaling to inhibit ROS-induced retinal injury, which indicated that targeting Cullin3 neddylation could be a promising treatment option for DR. Graphical Abstract Schematic diagram of the role of Cullin3 neddylation in DR and the effect of inhibition of Cullin3 neddylation with MLN4924 on DR.

Objective This study aimed to investigate the prevalence of glaucoma with associated factors in the rural populations of 10 provinces in China. Design A population-based cross-sectional study. Methods All participants aged 6 years or older from 10 provinces completed visual acuity testing, slit-lamp examination, ophthalmoscopy and non-contact tonometry. Glaucoma suspects underwent fundus photography, Goldmann applanation tonometry, visual field testing and gonioscopy. Glaucoma was determined according to the International Society of Geographical and Epidemiological Ophthalmology classification scheme. Associations of demographics and medical factors with glaucoma were assessed using multiple logistic regression models. Results From June 2017 to October 2018, 48 398 of 52 041 participants were included in the final analyses. The age-standardised prevalence of glaucoma was 1.7% (95% CI 1.55% to 1.78%) among the participants older than 6 years, which was 2.1% (95% CI 1.93% to 2.23%) in participants aged over 40 years. The constituent ratios of glaucoma were: 44.4% primary angle-closure glaucoma (PACG), 34.7% primary open-angle glaucoma, 2.6% congenital glaucoma and 18.3% other types of glaucoma. Increasing age, smoking, cerebral stroke, type 2 diabetes, higher education (college or more) and higher personal income were significant risk factors for PACG. The unilateral and bilateral blindness rates in the entire study population were 4.692% and 1.068%, respectively. A family history of glaucoma was a significant risk factor for the prevalence of glaucoma and blindness in at least one eye. Conclusions Rural populations have a high prevalence of glaucoma, which should be included in chronic disease management programmes in China for long-term care.

Phacoemulsification combined with intraocular lens (IOL) implantation is the international standard operation procedure for cataract and has been generalized worldwide. However, lens capsule opacification, one of the common complications after cataract surgery, impacts the recovery of patients’ visual function to a large extent. Lens capsule opacification has two types, anterior capsule opacification (ACO) and posterior capsule opacification (PCO), according to the location. There is not an accepted approach to treat ACO. Nd : YAG laser capsulotomy, the common treatment of PCO, can effectively improve the vision, but may cause a series of complications and is inappropriate for children who are too young to cooperate with this treatment. It is generally known that the responses of lens epithelial cells (LECs) after cataract surgery, including cell proliferation, migration, and epithelial-mesenchymal transition (EMT), play a key role in the pathogenesis of lens capsule opacification. Scholars found that substantial drugs can reduce the occurrence of lens capsule opacification by inhibiting, clearing, or killing LECs, and made great efforts as well as innovations on the exploration of drug species or modes of administration. This article is a systematic interpretation and elaboration about how to prevent lens capsule opacification after cataract surgery via different drugs.

Valsalva retinopathy and traumatic macular hole are common conditions, but macular hole secondary to Valsalva retinopathy is rarely reported.