Scimone Concetta, Alibrandi Simona, Scalinci Sergio Zaccaria, Trovato Battagliola Edoardo, D'Angelo Rosalia, Sidoti Antonina, Donato Luigi
Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98125 Messina, Italy.
Department of Biomolecular Strategies, Genetics and Avant-Garde Therapies, I.E.ME.S.T., 90139 Palermo, Italy.
Antioxidants (Basel). 2020 Nov 20;9(11):1154. doi: 10.3390/antiox9111154.
Inherited retinal dystrophies are characterized by photoreceptor death. Oxidative stress usually occurs, increasing vision loss, and oxidative damage is often reported in retinitis pigmentosa (RP). More than 300 genes have been reported as RP causing. In contrast, choroidal neovascularization (CNV) only occasionally develops in the late stages of RP. We herein study the regulation of RP causative genes that are likely linked to CNV onset under oxidative conditions. We studied how the endogenous adduct -retinylidene--retinylethanolamine (A2E) affects the expression of angiogenic markers in human retinal pigment epithelium (H-RPE) cells and a possible correlation with RP-causing genes. H-RPE cells were exposed to A2E and blue light for 3 and 6h. By transcriptome analysis, genes differentially expressed between A2E-treated cells and untreated ones were detected. The quantification of differential gene expression was performed by the Limma R package. Enrichment pathway analysis by the FunRich tool and gene prioritization by ToppGene allowed us to identify dysregulated genes involved in angiogenesis and linked to RP development. Two RP causative genes, and , can be associated with an increased risk of CNV development. Genetic analysis of RP patients affected by CNV will confirm this hypothesis.
遗传性视网膜营养不良的特征是光感受器死亡。通常会发生氧化应激，导致视力丧失加剧，视网膜色素变性（RP）中常出现氧化损伤。已报道有300多个基因可导致RP。相比之下，脉络膜新生血管（CNV）仅偶尔在RP晚期出现。我们在此研究在氧化条件下可能与CNV发病相关的RP致病基因的调控。我们研究了内源性加合物视黄叉 - 视黄基乙醇胺（A2E）如何影响人视网膜色素上皮（H-RPE）细胞中血管生成标志物的表达以及与RP致病基因的可能相关性。将H-RPE细胞暴露于A2E和蓝光下3小时和6小时。通过转录组分析，检测A2E处理细胞和未处理细胞之间差异表达的基因。使用Limma R软件包对差异基因表达进行定量。通过FunRich工具进行富集途径分析，并通过ToppGene进行基因优先级排序，使我们能够鉴定参与血管生成并与RP发展相关的失调基因。两个RP致病基因，和，可能与CNV发生风险增加有关。对受CNV影响的RP患者进行基因分析将证实这一假设。
