An analysis of samples obtained from a well-studied cohort of over 1,000 patients affected by type 1 diabetes (T1D) for 50 years or longer has identified a protein that protects against an eye condition called diabetic retinopathy (DR) - one of the most common consequences of diabetes - which impacts most diabetic patients after 20 years of living with the disease. Injecting the protein into rodents blocked DR without causing severe side effects, suggesting that preserving or administering the protein could help avoid debilitating eye damage in diabetic patients. Many patients with long-term diabetes develop eye disorders such as DR, which has become a leading cause of vision loss in developed countries. Interestingly, 35% of these patients never develop severe DR even after decades of being diabetic, suggesting they may harbor protective factors against such complications. To solve this mystery, Hishashi Yokomizo and colleagues turned to the Medalist cohort, a unique group of patients affected by T1D for at least 50 years. They compared protein profiles in the retina or vitreous fluid from a total of 43 deceased Medalist patients with either severe or no-to-mild DR, 21 non-Medalist patients with diabetes, and 13 non-diabetic controls. The authors discovered that the patients who were protected from advanced DR had higher levels of RBP3, a protein secreted by light-sensing cells in the eyes. Injecting RBP3 into the eyes of mice protected the animals against induced DR, and analysis showed that the protein inhibited the harmful effects of the growth factor VEGF and curtailed the secretion of inflammatory molecules in retinal cells. Future work should aim to replicate these results in people with short-term T1D or type 2 diabetes, the authors say.
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Science Translational Medicine