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

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.

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.

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.

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