Yun-Fan Zhou1,2, Lian-Jun Shi1,2, Jin Yao1,2, Ya-Nan Sun3, Kun Shan3, Qin Jiang1,2, Biao Yan3,4. 1. The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China. 2. The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China. 3. Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 4. NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, China.
Abstract
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.
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.
Authors: Monica Jong; Jost B Jonas; James S Wolffsohn; David A Berntsen; Pauline Cho; Danielle Clarkson-Townsend; Daniel I Flitcroft; Kate L Gifford; Annechien E G Haarman; Machelle T Pardue; Kathryn Richdale; Padmaja Sankaridurg; Milly S Tedja; Christine F Wildsoet; Joan E Bailey-Wilson; Jeremy A Guggenheim; Christopher J Hammond; Jaakko Kaprio; Stuart MacGregor; David A Mackey; Anthony M Musolf; Caroline C W Klaver; Virginie J M Verhoeven; Veronique Vitart; Earl L Smith Journal: Invest Ophthalmol Vis Sci Date: 2021-04-28 Impact factor: 4.799