Vitreous and Serum Measurements of Retinol Binding Protein 3 in the Clinical Evaluation of Diabetic Retinopathy

Abstract

Purpose : The Joslin 50-Year Medalist Study found that elevated photoreceptor-secreted Retinol Binding Protein 3 (RBP3) in the retina of individuals with chronic duration of type 1 diabetes is associated with long-term protection from advanced diabetic retinopathy (DR) independent of hyperglycemia. This is the first neuroretinal protein identified with protective attributes against the adverse effects of hyperglycemia on the retinal vasculature and neural retina. In this study we correlate DR severity and neural retinal layer thickness with vitreous and serum RBP3 within several cohorts with type 1 and type 2 diabetes.

Methods : We developed a sensitive (0.1-1 nM) and specific ELISA to assess vitreous and serum RBP3 concentrations in people with type 1 and type 2 diabetes from the Joslin Beetham Eye Institute, Medalist Study, and the FinnDiane study (a prospective longitudinal study of type 1 diabetes in Finland). Spectral-domain optical coherence tomography (Heidelberg Spectralis) images of the retina were segmented using automated segmentation software to correlate neural retinal layer thicknesses to RBP3 concentrations.

Results : Vitreous RBP3 concentration was associated with age (p=0.01), diabetes duration (p=0.02), high-density lipoprotein cholesterol (p<0.05), and DR severity (p<0.05) in Medalists (n=68), non diabetic controls (n=20), and type 1 and type 2 diabetic patients (n=24) with shorter diabetes duration (mean±SD 28±14.2 years). Decreased vitreous RBP3 concentration was associated with thinning of the inner nuclear layer, outer nuclear layer, and the photoreceptor layer (all p<0.0001). Serum RBP3 concentrations were 1000-fold less than those in vitreous, but correlated positively with vitreous RBP3 concentration (p<0.05). Decreased serum RBP3 concentration was associated with the baseline presence of laser photocoagulation (p=0.005) in the FinnDiane cohort. Repeated testing at 5 years demonstrated a strong correlation between baseline and 5 year RBP3 serum concentrations in the FinnDiane Study (r=0.77) and the Medalist Study (r=0.64, p=0.003).

Conclusions : Vitreous RBP3 concentration is associated with DR severity and thinning of specific neural retinal layers. Serum RBP3 concentration is associated with vitreous RBP3 concentration. These findings suggest that systemic measurement of RBP3 may be potentially useful in the clinical evaluation of DR.

This is a 2020 ARVO Annual Meeting abstract.