Original data1.

Diabetic retinopathy (DR) is a leading cause of blindness. We hypothesised that the long non-coding RNA RP11-502I4.3 may be involved in angiogenesis associated with DR. We investigated the role of RP11-502I4.3 in DR by examining its regulation of vascular endothelial growth factor (VEGF). We assessed differences in RP11-502I4.3 expression between the control group and streptozotocin-induced diabetic rats or high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). VEGF expression was measured with and without lentiviral vectors overexpressing RP11-502I4.3. We analysed the structural alterations related to DR after overexpressing RP11-502I4.3. Our analysis revealed that RP11-502I4.3 expression was lower in the retinas of diabetic rats and HG-stimulated HRMECs compared with normal glucose conditions. Overexpressing of RP11-502I4.3 resulted in decreased VEGF levels. Diabetic rats exhibited retinopathy characterised by thinning of the retinal layer thickness, structural changes in the inner and outer nuclear layers, a reduced count of retinal ganglion cells, and the presence of acellular capillaries. The proliferative activity, migration count, and tube formation ability of HG-treated HRMECs were significantly higher than those of the control group. However, these changes were inhibited by RP11-502I4.3 overexpression. Overexpression RP11-502I4.3 might inhibit retinopathy of diabetic rats and HG-induced angiogenesis by downregulating VEGF expression.

糖尿病视网膜病变（Diabetic retinopathy, DR）是引发失明的主要病因之一。我们提出假说：长链非编码RNA（long non-coding RNA）RP11-502I4.3可能参与DR相关的血管新生（angiogenesis）过程。本研究通过考察其对血管内皮生长因子（vascular endothelial growth factor, VEGF）的调控作用，探究了RP11-502I4.3在DR中的功能。我们对比了对照组与链脲佐菌素诱导的糖尿病大鼠（streptozotocin-induced diabetic rats），以及高糖（high glucose, HG）刺激下人视网膜微血管内皮细胞（human retinal microvascular endothelial cells, HRMECs）中RP11-502I4.3的表达差异。分别在转染过表达RP11-502I4.3的慢病毒载体（lentiviral vectors）与未转染该载体的条件下，检测VEGF的表达水平。我们还分析了RP11-502I4.3过表达后与DR相关的视网膜结构改变。本研究结果显示，与正常糖培养条件相比，糖尿病大鼠视网膜与HG刺激的HRMECs中RP11-502I4.3的表达水平显著降低。RP11-502I4.3过表达可导致VEGF水平下调。糖尿病大鼠的视网膜病变表现为视网膜层厚度（retinal layer thickness）变薄、内、外核层（inner and outer nuclear layers）结构异常、视网膜神经节细胞（retinal ganglion cells）数量减少，以及无细胞毛细血管（acellular capillaries）的出现。经HG处理的HRMECs，其增殖活性（proliferative activity）、迁移数（migration count）与管形成能力（tube formation ability）均显著高于对照组；但上述异常改变可被RP11-502I4.3过表达所抑制。综上，RP11-502I4.3过表达可能通过下调VEGF的表达，抑制糖尿病大鼠的视网膜病变以及HG诱导的血管新生。