The role of pericyte in ocular vascular diseases.

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

Circular RNA-ZBTB44 regulates the development of choroidal neovascularization.

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.

Microarray Analysis of circRNA Expression Pattern in Corneal Neovascularization.

PURPOSE: To identify differentially expressed circular RNAs (circRNAs) in corneal neovascularization. METHODS: We established an alkali burn-induced corneal neovascularization model and performed circRNA expression profiling to identify differentially expressed circRNAs between avascular corneas and vascularized corneas. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses of the host genes of dysregulated circRNAs were performed to determine the related biological modules and pathological pathways. Real-time polymerase chain reactions were performed to detect the expression pattern of circRNAs in the clinical samples. In vitro experiments were performed to determine the role of circRNAs in vascular endothelial angiogenic effects. RESULTS: Two hundred twenty-nine circRNAs were differentially expressed between avascular corneas and vascularized corneas. The host genes of dysregulated circRNAs were targeted to cell cycle (biologic process), cytoplasm (cellular component), and protein binding (molecular function). Rap1 signaling was identified as the most enriched signaling pathway. Clinical studies showed that the human ortholog of cZFP609 and cKifap3 was dysregulated in the vascularized human corneas. cKifap3 silencing facilitated vascular endothelial angiogenic effects by regulating endothelial cell proliferation, migration, and tube formation. CONCLUSIONS: This study suggests that circRNAs are involved in the pathogenesis of corneal neovascularization. cZFP609 and cKifap3 may serve as promising targets for the treatment of corneal neovascularization.