Development of a biostable and biosafe vitreous substitute is highly desirable, but remains a grand challenge. Herein, we propose a novel strategy for constructing a readily administered vitreous substitute based on a thiol-acrylate clickable polyzwitterion macromonomer. A biocompatible multivinyl polycarboxybetaine (PCB-OAA) macromonomer is designed and synthesized, and mixed with dithiothreitol (DTT) via a Michael addition reaction to form a hydrogel in vitreous cavity. This resultant PCB-OAA hydrogel exhibits controllable gelation time, super anti-fouling ability against proteins and cells, excellent biocompatibility, and approximate key parameters to human vitreous body including equilibrium water content, density, optical properties, modulus. Remarkably, outperforming clinically used silicone oil in biocompatibility, this rapidly formed hydrogel in the vitreous cavity of rabbit eyes remains stable in vitreous cavity, showing an appealing ability to prevent significantly inflammatory response, fibrosis and complications such as raised intraocular pressure (IOP), and cataract formation. This zwitterionic polymer hydrogel holds great potential as a vitreous substitute.

Background: To compare the anterior biometrics in eyes with secondary acute angle closure induced by occult lens subluxation (ASAC-LS), misdiagnosed as acute primary angle closure (APAC) at the first visit with APAC, chronic primary angle closure glaucoma (CPACG), and cataract. Methods: This retrospective case study included 17 eyes with angel closure due to occult LS, who were misdiagnosed as APAC on their first visit, 56 APAC eyes, 54 CPACG eyes, and 56 cataract eyes. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AD) and lens thickness (LT) were recorded. Lens position (LP), relative lens position (RLP), corrected lens position (CLP) were calculated. Quantitative data were subject to one-way analysis of variance and correlation analysis. Categorical data were analyzed using the chi-squared test. Receiver operating characteristic (ROC) curves were plotted to obtain a suitable cutoff value of ocular biometrics. Results: The ASAC-LS patients had a longer ocular axial length than APAC and CPACG patients. Central corneal thickness of the ASAC-LS patients was not significantly different from APAC patients, but was significantly different from CPACG and cataract patients. The APAC patients had the smallest ACD, while the ASAC-LS patients had the smallest AD. The ASAC-LS patients had the largest lens thickness. According to ROC curve analysis, RLP, ACD, AD, CLP, LP had high power of discrimination. Conclusions: This study revealed that LS secondary PAC patients had a shallower AD, thicker CCT comparing to those of APAC, CPACG and cataract patients. For patients with acute angle-closure glaucoma, it is necessary to exclude lens zonula relaxation. Trial registration: NCT03752710, retrospectively registered.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Purpose: To observe the protective effects and underlying mechanisms of dl-3-n-butylphthalide (NBP) against H₂O₂-induced oxidative damage in retinal Müller cells. Methods: Cultured human Müller cell line (MIO-M1line) were exposed to H₂O₂ for 2 hours. Cell survival was evaluated by Calcein AM cell viability assay. Dichlorofluorescein diacetate (DCFDA) + endoplasmic reticulum (ER) red fluorescent probe (ER-Tracker Red) staining was used to observe the expression level of reactive oxygen species (ROS) in ER of cells. Mitochondrial membrane potential detection (JC-1) was used to observe cell membrane potential change and early apoptosis. Cell apoptosis was detected by Hoechst33258 staining. The expressions of Nrf2, HO-1 were documented by cell Immunofluorescence staining and Western blot analysis. Results: NBP effectively improved the survival ability of Müller cells shown by MTT assay. NBP effectively alleviated the morphological and apoptotic changes induced by H₂O₂ stimulation by Calcein AM assay, HE staining, Hoechst 33258, JC-1 staining. H₂O₂ induction increased the expression level of ROS, whereas, the treatment with NBP could remarkably lower the expression level of ROS. Cell immunofluorescence staining indicated that the fluorescence staining intensity of HO-1 in the NBP group was significantly higher than that in the control group. While the western blotting results showed that the expression level of HO-1 could be increased by NBP in a time-dependent manner. The translocation of Nrf2 in nuclei was observed within 2 h and Nrf2 was identified in nuclei for up to 48 h. Conclusions: Our study demonstrated that NBP had a protective effect on H₂O₂-induced cytotoxicity in retinal Müller cells in vitro and that it was a potent activator of Nrf2 and HO-1signaling.