Retinol Binding Protein-4 and Galectin-3 Levels in Type II Diabetes: Their Impact on Retinopathy Risk.

Abstract

Purpose: Retinol binding protein-4, a lipocalin family member, and galectin-3, a lectin family member, link their potential role in modulating glucose metabolism and inflammation. This study aims to explore retinol binding protein-4 and galectin-3's role as the disease progresses from prediabetes to diabetic retinopathy and to ascertain whether these variables could serve as risk or diagnostic indicators for diabetic retinopathy.

Methods: This study includes 100 patients divided into three groups, diabetic retinopathy (n = 39), type 2 diabetes mellitus (n = 41), and prediabetes (n = 21), based on inclusion and exclusion criteria. Serum levels of retinol binding protein-4 and galectin-3 were assessed by sandwich ELISA. Immunofluorescence analysis was employed to localize retinol binding protein-4 and galectin-3 in the retinal layers. The increase in serum retinol binding protein-4 levels was validated by quantitative western blot analysis. The HDOCK tool was used to identify the protein-protein interactions between retinol binding protein-4 and VEGF.

Results: Serum retinol binding protein-4 levels were higher in diabetic retinopathy and type 2 diabetes mellitus compared to prediabetes (p < 0.0001). Further, western blot analysis confirmed a significant twofold increase in diabetic retinopathy compared to the prediabetes groups (p = 0.0423). Serum galectin-3 levels were insignificantly higher in diabetic retinopathy and type 2 diabetes mellitus when compared to prediabetes. The receiver operating characteristic curve analysis, the area under the curve values, also indicates that serum retinol binding protein-4 had acceptable performance (area under the curve: 0.7965 and 0.9007) for the comparison between prediabetes vs. type 2 diabetes mellitus and prediabetes vs. diabetic retinopathy, respectively, as compared to serum galectin-3 (area under the curve: 0.6961 and 0.7008). In the IF analysis, retinol binding protein-4 localization was more common in the photoreceptor region and the retina vessels, whereas galectin-3 was distributed in the ganglion cell layer of the retina. The strong binding between retinol binding protein-4 and the VEGFA and VEGFB isoforms was observed during the protein-protein interaction study.

Conclusion: This study reveals that retinol binding protein-4 seems to be a diagnostic marker for diabetic retinopathy, which requires further investigation.