Association of Aqueous Retinol Binding Protein 3 (RBP3) and Diabetic Retinopathy Severity

Abstract

Purpose : Although laser photocoagulation and anti-VEGF treatment are effective for advanced diabetic retinopathy (DR), there remains an important need to identify markers and therapeutic targets for DR worsening at earlier stages. Retinol-binding protein 3 (RBP3) is a potential protective factor against DR in the vitreous and retina of individuals with type 1 diabetes for 50 years or longer (Joslin Medalist Study). This study aims to evaluate the association between RBP3 in the aqueous fluid and DR severity in patients with type 1 and type 2 diabetes.

Methods : Aqueous samples were obtained from diabetic patients during cataract surgery at the Joslin Beetham Eye Institute (N=30) and from post-mortem eyes (N=101) of Medalists. RBP3 concentration was measured in all samples using a specific ELISA assay. Individual retinal layer thicknesses in the foveal 1x1mm area were measured by optical coherence tomography (Spectralis) with automated layer segmentation (Heidelberg v6.0c, Germany, N=45).

Results : 131 participants had a mean age of 73 ± 8 years, A1c 7.4 ± 1%, 84% type 1 diabetes, and 72% female. RBP3 levels in aqueous samples decreased with increasing DR severity from mild DR (median 0.7nM ± 0.2) to proliferative DR (PDR, 0.5nM ± 0.2, P=0.001). Aqueous RBP3 concentrations in Beetham Eye Institute and Medalists samples were similar for eyes with PDR (P=0.11). Aqueous RBP3 concentration was inversely associated with the presence of pan-retinal laser photocoagulation scars (β estimate -22.0, 95% CI -31.9;-12.0, P<0.0001), but not with A1c (P=0.60). RBP3 concentrations in aqueous were well correlated between fellow eyes (r=0.65, P<0.0001). RBP3 concentrations in aqueous and vitreous samples were correlated within the same individual (r=0.32, P=0.003, N=89). On average, RBP3 concentration in aqueous was 12-fold lower compared to vitreous samples. Higher aqueous concentrations were associated with increased thickness of the ganglion cell layer (β estimate 0.002, 95% CI 0.0019;0.0023, P<0.0001) and inner nuclear layer (0.0026, 0.0025;0.0028, P<0.0001), and decreased thickness of the retinal pigment epithelium (-0.001, -0.0017;0.0003, P=0.004).

Conclusions : These findings suggest that RBP3 concentrations in aqueous and vitreous fluids are correlated and reduced in people with advanced DR, supporting its potential use as a biomarker and therapeutic agent in people with type 1 and type 2 diabetes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.