Association of Peroxisome Proliferator-Activated Receptors (PPARs) with Diabetic Retinopathy in Human and Animal Models: Analysis of the Literature and Genome Browsers.

Abstract

Diabetic retinopathy (DR) is a condition that develops after long-lasting and poorly handled diabetes and is presently the main reason for blindness among elderly and youth. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are involved in carbohydrate and fatty-acid metabolism and have also been associated with DR. Three PPAR isoforms are known: PPARG, PPARA, and PPARD. In the present study, we retrieved articles reporting associations between PPARs and DR from PubMed database and compiled the data in two catalogues, for human and animal models. Extracted data was then complemented with additional relevant genomic information. Seven retrieved articles reported testing an association between PPARs with DR in human. Four of them concluded association of PPARG and PPARA with DR in European and Asian populations, having a protective role on DR development. One study reported pathogenic role of PPARG, while two articles reported no association between PPARG and DR among Indian and Chinese populations. Six retrieved articles reported testing of involvement of PPARG and PPARA in DR in animal models, including mouse and rat. The review includes case-control studies, meta-analysis, expression studies, animal models, and cell line studies. Despite a large number of documented sequence variants of the PPAR genes available in genome browsers, researchers usually focus on a small set of previously reported variants. Data extraction from Ensembl genome browser revealed several sequence variants with predicted deleterious effect on protein function which present candidates for further experimental validation. Results of the present analysis will enable more holistic approach for understanding of PPARs in DR development. Additionally, developed catalogues present a baseline for standardized reporting of PPAR-phenotype association in upcoming studies.