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Ai Ling Wang, Michael A. Grassi; Role Of FAM18B In Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2579.
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A genome-wide association study performed by our group has implicated FAM18B, a gene of unknown function, in the pathogenesis of severe diabetic retinopathy. We sought to explore the function and potential role of FAM18B in diabetic retinopathy.
Immunohistochemical labeling of FAM18B was examined in posterior segments of postmortem human eye samples using antibodies specific for FAM18B. For functional evaluation, cultured human retinal microvascular endothelial cells (HRMECs) and a rat retinal endothelial cell line (TR-iBRB) were exposed to advanced glycation end products (AGEs) (100 ug/mL) for 24hrs. Expression levels of FAM18B were measured. In order to explore clinical relevance and assess correlation with disease severity, human peripheral blood samples were collected from subjects with diabetes (proliferative diabetic retinopathy (PDR) (n=8) or no diabetic retinopathy (n=9)). White blood cells were labeled with antibodies specific for VEGFR2 and CD34, markers for endothelial progenitor cells (EPCs) which are the major contributors to pathologic neovascularization in diabetic retinopathy. The double positive cells of VEGFR2 and CD34 were isolated by flow cytometry. Expression levels of FAM18B were measured in isolated EPCs by quantitative PCR.
FAM18B is specifically located in vascular endothelial cells, both in neural retina and choroid. In-vitro experiments in both TR-iBRB and HRMECs show FAM18B to be significantly decreased in response to AGEs treatment (p=0.04 and p=0.03, respectively). FAM18B gene expression was also significantly down-regulated in EPCs from PDR patients compared to subjects without diabetic retinopathy (p=0.001).
In conjunction with the genetic association studies this work suggests that FAM18B may play a role in the pathogenesis of diabetic retinopathy given its presence in retinal endothelial cells, response to AGEs, and differential regulation in individuals with PDR.
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