@article{4ff9ada613ce4212a28e8e8b4e252def,
title = "Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy",
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 M{\"u}ller 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.",
author = "Hisashi Yokomizo and Yasutaka Maeda and Kyoungmin Park and Clermont, {Allen C.} and Hernandez, {Sonia L.} and Ward Fickweiler and Qian Li and Wang, {Chih Hao} and Paniagua, {Samantha M.} and Fabricio Simao and Atsushi Ishikado and Bei Sun and Wu, {I. Hsien} and Sayaka Katagiri and Pober, {David M.} and Tinsley, {Liane J.} and Avery, {Robert L.} and Feener, {Edward P.} and Kern, {Timothy S.} and Keenan, {Hillary A.} and Aiello, {Lloyd Paul} and Sun, {Jennifer K.} and King, {George L.}",
note = "Funding Information: We thank the Medalists patients and their families, the individuals who donated eye samples, the clinicians at the Beetham Eye Institute, the National Disease Research Interchange (NDRI), and the California Retina Consultants (R.L.A.) for coordinating eye donations, the Medalist staff (S. Turek, S. D'Eon, and S. Hastings), the Proteomics Core staff (X. Chen and J. Woodward), and B. Kunkemoeller, Y.-H. Tseng, and S. Kissler at the JDC. This work was supported by grants from the NIH NEI R01EY026080-01 to G.L.K., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NIH 1DP3DK112192-01 to G.L.K. and NIH 1DP3DK094333-01 to G.L.K. and H.A.K., and NIDDK Diabetes Research Center grant P30DK036836; grants from the Juvenile Diabetes Research Foundation (JDRF) JDRF 8-2005-358 (G.L.K.), JDRF 18-2008-363 (G.L.K.), JDRF17-2011-474 (H.A.K.), and JDRF17-2013-310 (H.A.K.); and a grant from the Beatson Foundation Gift and the Dianne Nunnally Hoppes fund. H.Y. received the research fellowship from Manpei Suzuki Diabetes Foundation, Japan, and Mary K. Iacocca Foundation, USA. G.L.K. had held a basic research grant from Sanofi pharmaceutical company during part of this study. The support from Sanofi was for renal studies and not applicable to the studies on RBP3 or eyes in the Medalist study. Publisher Copyright: {\textcopyright} 2019 The Authors, some rights reserved.",
year = "2019",
doi = "10.1126/scitranslmed.aau6627",
language = "English",
volume = "11",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "499",
}
