Expression of Pro-Angiogenic Markers Is Enhanced by Blue Light in Human RPE Cells

Abstract

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 N-retinylidene-N-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, AHR and ROM1, can be associated with an increased risk of CNV development. Genetic analysis of RP patients affected by CNV will confirm this hypothesis.

Eye Fixation-Related Potentials during Visual Search on Acquaintance and Newly-Learned Faces

“…For instance, future work can aim to find electrophysiological responses in patients with problems of face recognition [ 37 ] using EFRPs, as it has been shown that visual evoked potentials (VEPs) with reduced amplitude and delayed latency reflect the dysfunction in visual processing [ 38 ]. Moreover, it would be plausible to associate specific characteristics of EFRPs during visual processing with more biological mechanisms to make integrated accounts for neurodegenerative disorders such as retinal dystrophies [ 39 , 40 ].…”

Antioxidant Defenses in the Human Eye: A Focus on Metallothioneins

“…Even more, the MT antioxidant role was evidenced by the former studies of Lu et al, 2002 [ 243 ] showing that elevation of MT levels by transfection of RPE cells (D407 spontaneously immortalized cell line) protected against toxic levels of cadmium [ 299 ], heme- and iron-induced oxidation and UV light-induced apoptosis. In this regard, the combination of N-retinylidene-N-retinylethanolamine (A2E) and blue light permitted to study causative genes of retinitis pigmentosa using primary cultures of RPE cells under oxidative conditions, showing altered expression of aryl hydrocarbon receptor (AHR) and retinal outer segment membrane protein 1 (ROM1), but also other genes, including MTs [ 300 ]. Similarly, the effect of A2E-induced oxidative stress on human RPE cells determined relevant differences in gene expression and splicing events contributing to elucidate molecular mechanisms linking oxidative stress and retinal dystrophies [ 301 ].…”

Association of UCP1 and UCP2 variants with diabetic retinopathy susceptibility in type-2 diabetes mellitus patients: a meta-analysis

“…The elevation of oxidative stress has been suggested contributing to the development of DM complications [ 5 ], which is caused by reactive oxygen species (ROS) overproduction, mainly the mitochondrial ROS [ 5 – 7 ]. Excessive ROS resulted from hyperglycemia causes retinal mitochondrial dysfunction with serious damage to the oxidative phosphorylation complexes and abolished adenosine triphosphate biosynthesis [ 8 ], and induces capillary endothelial cell apoptosis, which subsequently leads to the dysregulation of the angiogenesis-related genes [ 9 ] and diabetic microvascular complications, including DR [ 10 , 11 ]. Ion channels physiologically play a role in signal transmission and visual processing, but also link to induced oxidative stress and significantly contribute to a wide spectrum of ocular diseases [ 12 ].…”