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sulochana natarajan, Subbulakshmi Chidambaram, Vidhya Srinivasan, Karthikka Palanisamy, Pukhraj Rishi, Radhakrishnan Selvi; Can Adiponectin be a Therapeutic Target for Proliferative Diabetic Retinopathy?. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1145.
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Adiponectin(APN) is a protein hormone having antidiabetic and anti inflammatory properties. Its presence, in ocular tissues, has been postulated, to have escaped from circulation due to the dysfunctional BRB in retinal diseases. The purpose of this study is to understand the origin of intraocular APN and its receptors, precisely measure vitreous APN in PDR and macular hole (MH), study its role in, in vitro angiogenesis and to screen small molecules, which can stimulate APN synthesis.
All human studies were done with approval from IRB and consent of the participants. Tissues derived from donor eye balls were used for qPCR, immuno staining and western blot analysis. Vitreous samples were obtained from patients who underwent vitrectomy surgery for PDR and MH and used for APN measurement by ELISA. Human retinal endothelial cells (hREC), human choroidal endothelial cells (hCEC) and HUVEC were used for in vitro angiogenesis studies. Human adipocytes, hCEC and hREC were used for screening small molecules including amino acids and fatty acids, in order to select the one which stimulates APN secretion.
Expression of APN, AdipoR1 and AdipoR2 in retina, choroid, iris more specifically in the neural retina, photoreceptors, and endothelium was unambiguously identified by qPCR, immunostaining and western blot analysis. APN level in vitreous of patients with PDR (n=29) was found to be significantly (p<0.000) elevated, 91.1±17.7 ng/mL when compared to 0.32±0.31 ng/mL in vitreous from patients who underwent MH surgery (n=11). Moreover, Epiretinal membranes from PDR were also stained positive for APN and its receptors. Further, we transfected primary HUVEC, hREC and hCEC with APN pAcGFP1-C1 and performed functional studies. Interestingly, APN inhibited tube formation and migration of hREC, hCEC and HUVEC even in the presence of VEGF and PDR vitreous which suggested a potent antiangiogenic property for APN. Among the compounds screened, phenylalanine significantly increased APN level upto 10 folds in all three types of cells.
Our experiments identified expression of APN and its receptors in ocular tissues. Increased levels of APN in vitreous of PDR patients and its antiangiogenic effects suggest a potential compensatory role for APN in this disease. Link between the amino acids and APN secretion should be further studied for their therapeutic use.
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