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.
Highlights
Diabetic retinopathy (DR) is a condition that develops due to bad glycemic control in subjects with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM)
We developed two tables consisting of data extracted from 13 retrieved articles published between 1/2012 and 12/2017 reporting associations between Peroxisome proliferator-activated receptors (PPARs) polymorphisms and DR in human (Table 1) and animal models (Table 2) (Figure 2)
Six studies were performed in animal models, including four articles describing involvement of Peroxisome proliferator-activated receptor alpha (PPARA) in DR and two involvement of Peroxisome proliferator-activated receptor gamma (PPARG) in DR
Summary
Diabetic retinopathy (DR) is a condition that develops due to bad glycemic control in subjects with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Long-lasting poor blood glucose control, smoking, and hypertension can contribute to DR development [1, 2]. The disease progresses from nonproliferative (NPDR) to proliferative (PDR) stage where at first microvascular irregularities such as hemorrhage, ischemia, and microaneurysms lead to neoangiogenesis [2]. Microvascular changes start due to lower concentrations of oxygen in the retina of the eye after the disease progresses, and at final stages, PDR can lead to vision loss. Diabetic retinopathy had become the main reason for blindness in American adults. In year 2012, there were approximately 93 million people living with diabetic retinopathy, 17 million with PDR, and 21 with diabetic macular edema, and the number is expected to increase in the future [3, 4]
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