June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Association of Vitreous Retinol Binding Protein 3 with Diabetic Retinopathy in Type 1 and Type 2 Diabetes
Author Affiliations & Notes
  • Ward Fickweiler
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Hyunseok Park
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Kyoungmin Park
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Tahani Boumenna
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
  • John Gauthier
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
  • I-Hsien Wu
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Jerry Cavallerano
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Lloyd Paul Aiello
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Jennifer K Sun
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • George Liang King
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ward Fickweiler, None; Hyunseok Park, None; Kyoungmin Park, None; Tahani Boumenna, None; John Gauthier, None; I-Hsien Wu, None; Jerry Cavallerano, None; Lloyd Aiello, Kalvista (C), Kalvista (I), Novo Nordisk (C), Regeneron (C); Jennifer Sun, Adaptive Sensory Technologies (F), Boehringer Ingelheim (F), Kalvista (F), Novo Nordisk (R), Optovue (F), Roche (F), Roche (R); George King, None
  • Footnotes
    Support  National Institutes of Health; NEI (R01EY026080-01), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DP3 DK094333-01), Juvenile Diabetes Research Foundation (JDRF) (17-2013-310), Beatson Foundation Gift, Dianne Nunnally Hoppes fund
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1114. doi:
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    • Get Citation

      Ward Fickweiler, Hyunseok Park, Kyoungmin Park, Tahani Boumenna, John Gauthier, I-Hsien Wu, Jerry Cavallerano, Lloyd Paul Aiello, Jennifer K Sun, George Liang King; Association of Vitreous Retinol Binding Protein 3 with Diabetic Retinopathy in Type 1 and Type 2 Diabetes. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1114.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The Joslin 50-Year Medalist Study identified elevated concentrations of retinal specific protein, Retinol Binding Protein 3 (RBP3) in people with 50 years or longer duration of type 1 diabetes and no to mild non-proliferative diabetic retinopathy (NPDR), suggesting potential to neutralize toxic effects of hyperglycemia on the vascular and neuronal retina. This study correlated RBP3 levels in the vitreous with diabetic retinopathy (DR) severity and progression in a large group of people with type 1 and type 2 diabetes.

Methods : Vitreous samples (n=213) were obtained during vitreoretinal surgery at the Joslin Beetham Eye Institute (n=58) and from post-mortem eyes (n=155) of Medalists. RPB3 concentration was measured by two self-developed ELISAs using either colorimetric or luminescent assays with a linear detection range of 10 pM to 15 nM and inter-experimental variation of <5%.

Results : Elevated vitreous RBP3 concentration was associated with less severe DR in all eyes (p<0.0001), post-mortem Medalist specimens (p<0.0001) and surgical samples from type 1 and type 2 diabetic patients with shorter diabetes duration (mean±SD 26.5±12.7 yrs, p=0.03). RBP3 concentration in subjects with no diabetes (NDM, median: 22.4 nM) and no to mild NPDR (15.7 nM) were increased compared to moderate-severe NPDR (8.2 nM, p<0.01 and p=0.01, respectively), active proliferative DR (PDR, 8.4 nM, p<0.0001 and p=0.0003, respectively) and quiescent PDR (3.5 nM, p<0.0001, both). Vitreous RBP3 concentration was associated with age (point estimate 0.06, p=0.008), diabetes duration (0.04, p=0.05), triglycerides (-0.01, p<0.05), neuropathy (-0.07, p=0.02), albumin/creatinine ratio (-0.01, p<0.0001), and panretinal laser (-1.06, p=0.01), but not with A1c (p=0.68). There was no difference in RBP3 concentration between people with type 1 and type 2 diabetes (p=0.44). Vitreous RBP3 concentrations were highly correlated between fellow eyes (r=0.86, p<0.0001). Further, in participants with longitudinal follow up, higher RBP3 concentrations were associated with reduced risk of PDR development over time (n=34, p<0.001).

Conclusions : These data suggest that higher RBP3 concentration in the vitreous is associated with less severe DR and slower rates of progression to PDR, supporting its therapeutic potential for prevention of DR worsening in people with diabetes.

This is a 2021 ARVO Annual Meeting abstract.

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