Background: To comprehensively investigate risk factors for proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched until May 22, 2023. Risk factors included demographic and disease-related risk factors. Odds ratios (ORs) and weighted mean differences (WMDs) were used as the effect sizes, and shown with 95% confidence intervals (CIs). Sensitivity analysis was conducted. The protocol was registered with PROSPERO (CRD42022378652). Results: Twenty-two studies of 13,875 subjects were included in this systematic review and meta-analysis. Increased age was associated with a higher risk of postoperative PVR (pooled WMD = 3.98, 95%CI: 0.21, 7.75, P = 0.038). Smokers had a higher risk of postoperative PVR than non-smokers (pooled OR = 5.07, 95%CI: 2.21–11.61, P<0.001). Presence of preoperative PVR was associated with a greater risk of postoperative PVR (pooled OR = 22.28, 95%CI: 2.54, 195.31, P = 0.005). Presence of vitreous hemorrhage was associated with a greater risk of postoperative PVR (pooled OR = 4.12, 95%CI: 1.62, 10.50, P = 0.003). Individuals with aphakia or pseudophakia had an increased risk of postoperative PVR in contrast to those without (pooled OR = 1.41, 95%CI: 1.02, 1.95, P = 0.040). The risk of postoperative PVR was higher among patients with macula off versus those with macula on (pooled OR = 1.85, 95%CI: 1.24, 2.74, P = 0.002). Extent of RD in patients with postoperative PVR was larger than that in patients without (pooled WMD = 0.31, 95%CI: 0.02, 0.59, P = 0.036). Patients with postoperative PVR had longer duration of RD symptoms than those without (pooled WMD = 10.36, 95%CI: 2.29, 18.43, P = 0.012). Conclusion: Age, smoking, preoperative PVR, vitreous hemorrhage, aphakia or pseudophakia, macula off, extent of RD, and duration of RD symptoms were risk factors for postoperative PVR in patients undergoing RD surgery, which may help better identify high-risk patients, and provide timely interventions.

Diabetic retinopathy (DR) ranks among the primary causes of adult blindness globally. Oxidative stress and mitochondrial dysfunction play a critical role in the progression of DR. Mounting data indicated that small extracellular vesicles (sEVs) of mesenchymal stem cell (MSC) have the ability to transport bioactive chemicals to target cells, leading to changes in their phenotype. Nevertheless, it remains elusive how MSC-derived sEVs regulate oxidative stress and mitochondrial function in DR. MSC-sEVs was intravitreally injected to streptozotocin (STZ)-treated Sprague-Dawley rats to assess the therapeutic effects on DR. The underlying regulatory mechanism was investigated by coculturing advanced glycation end-products (AGEs)-induced rat Müller cells with/without PTP1B overexpression with MSC-sEVs in vitro, with or without miR-125a-5p suppression. Intravitreal injection of MSC-sEVs improved histological morphology and blood-retinal barrier function, alleviated Müller gliosis, decreased PTP1B expression, redox stress and apoptosis in retina of diabetic rat. MSC-sEVs decreased the accumulation of ROS and improved the structure and function of mitochondria of Müller cells with AGEs treatment. Mechanically, MSC-sEVs activated the mitophagy of AGEs-treated Müller cells, represented by an increased expression of the LC3II/LC3I ratio, TOM20, PINK1 and Parkin along with a decreased expression of P62. Importantly, miR-125a-5p inhibitor abolished the protective effects of MSC-sEVs. Furthermore, the overexpression of PTP1B in Müller cells reduced the effects of MSC-sEVs. These findings suggested that miR-125a-5p of MSC-sEVs alleviates Müller cells injury in DR by modulating PINK1/Parkin-mediated mitophagy via PTP1B pathway.

As the predominant microvascular complication of diabetes mellitus that leads to blindness, diabetic retinopathy (DR) still presents a challenge due to the scarcity of effective therapeutic approaches, particularly in its early stage. Here, we observed that the expression of the mitochondrial open-reading-frame of the 12 S rRNA-c (MOTS-c), a mitochondrial-derived peptide, was predominantly localized in retinal endothelial cells. Thus, we combined genetic and pharmacological approaches in vivo and in vitro to explore whether vascular endothelial damage in DR is involved in MOTS-c dysregulation and its underlying mechanism. High glucose exposure reduced the expression of MOTS-c in retinal vasculature. While MOTS-c treatment protected endothelial barrier and ameliorated mitochondrial dysfunction in human retinal endothelial cells with high-glucose-induced injury and streptozotocin-induced diabetic mouse model. Furthermore, in vitro experiments were used to explore the underlying molecular mechanisms for rescuing vascular endothelial damage of MOTS-c. Transcriptomic analyses and lipidomic analyses showed that MOTS-c increased the phospholipase A2 activity and regulated phospholipid metabolism. Among the differentially expressed genes associated with upregulated phospholipase A2 activity, phospholipase A2 group VI (PLA2G6) exhibited the most significant upregulation following MOTS-c treatment. PLA2G6-mediated lipid peroxide degradation served as a primary mediator of protecting the retinal endothelial barrier during MOTS-c treatment, while knockdown of PLA2G6 blocked the protective effect of MOTS-c against vascular endothelial damage in vitro and in vivo. Taken together, our findings identified a novel role of MOTS-c dysregulation mediating vascular endothelial damage in DR and that MOTS-c supplementation was a potential therapeutic approach to regulating phospholipid homeostasis and protecting the endothelial barrier via PLA2G6 against DR.