Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy

Hisashi Yokomizo, Yasutaka Maeda, Kyoungmin Park, Allen C. Clermont, Sonia L. Hernandez, Ward Fickweiler, Qian Li, Chih Hao Wang, Samantha M. Paniagua, Fabricio Simao, Atsushi Ishikado, Bei Sun, I. Hsien Wu, Sayaka Katagiri, David M. Pober, Liane J. Tinsley, Robert L. Avery, Edward P. Feener, Timothy S. Kern, Hillary A. KeenanLloyd Paul Aiello, Jennifer K. Sun, George L. King

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells. Elevated expression of photoreceptorsecreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.

Original languageEnglish
Article numbereaau6627
JournalScience Translational Medicine
Volume11
Issue number499
DOIs
Publication statusPublished - 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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