Long noncoding RNAs (lncRNAs) have important roles in various biological processes. Our previous work has revealed that dedifferentiation of retinal pigment epithelium (RPE) cells contributes to the pathology of age-related macular degeneration (AMD). Herein, we show roles of lncRNAs in RPE differentiation. We used microarray to identify lncRNA expression profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived RPE cells. A total of 217 differentially expressed lncRNAs along with the differentiation were initially identified, among which 13 lncRNAs showed a consistent fold change of over 2. LncRNA ZNF503-AS1, located in the cytoplasm of RPE cells, was found consistently upregulated along with RPE differentiation, and downregulated in the RPE-choroid of AMD patients. In vitro study further suggested that ZNF503-AS1 insufficiency could inhibit RPE differentiation, and promote its proliferation and migration. As ZNF503-AS1 is transcribed from the antisense strand of the ZNF503 gene locus, we further revealed its regulatory role in ZNF503 expression. ZNF503-AS1 was reversely correlated with ZNF503 expression. Our results also suggested that ZNF503 could inhibit RPE differentiation, and promote its proliferation and migration. Thus, ZNF503-AS1 potentially promotes RPE differentiation through downregulation of ZNF503 expression. In addition, nuclear factor-κB was recognized as a potential upstream transcript factor for ZNF503-AS1, which might participate in promoting RPE differentiation by regulating the expression of ZNF503-AS1. Taken together, our study identifies a group of RPE differentiation relevant lncRNAs, and the potential role of ZNF503-AS1 in the pathology of atrophic AMD, which might help with the intervention of AMD patients.

Purpose: To compare the efficacy of a modified perfluorocarbon liquid–assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes. Methods: This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid–assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery. Results: Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044). Conclusion: The perfluorocarbon liquid–assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.