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Riyaz Mohamed, Ahmed Ibrahim, Nehal M El-Sherbiny, Mohamed Al-Sayed Al-Shabrawey, Amany M Tawfik; Role of N-methyl-D-aspartate receptor activation in Blood-Retinal barrier dysfunction: Potential role in Diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4047.
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© ARVO (1962-2015); The Authors (2016-present)
Homocysteine (Hcy) is a risk factor for neurodegenerative and cardiovascular diseases and has been reported to be elevated in patients with diabetic retinopathy (DR). Our recent studies showed that Hcy induced retinal ischemia, neovascularization and Blood-Retinal Barrier dysfunction (BRB). The current study is aiming to investigate the role of N-methyl-D-aspartate receptor (NMDAr) in Hcy induced BRB dysfunction.
We confirmed the expression of NMDAr in Human Retinal Endothelial Cells (HRECs) by real-time polymerase chain reaction (qPCR) in comparison with Retinoblastoma cell line as a positive control. In addition, HRECs treated with or without different concentrations of Hcy (20, 50 and 100mM) were subjected to Evaluation of NMDAr activation in by Western blot (WB) and immunofluorescence (IF). FITC–Dextran flux permeability assay in presence and absence an NMDAr antagonist (MK801, 25µM). Furthermore, mice with increased level of Hcy (cbs+/-) and different mouse models of diabetes (Streptozotocin (STZ), db/db and Akita) mice were evaluated for NMDAr activation in retinal cryosections by Immunofluorescence (IF).
NMDAr is expressed in HRECs and WB and IF analysis showed that Hcy significantly increased NMDAr expression in HRECs in a dose-dependent manner, increased FITC-dextran leakage in HRECs which was rescued by NMDAr antagonist MK801. Furthermore, NMDAr expression was increased in cbs+/- mice retina as well as the diabetic mice retinal sections in comparison to control mice.
Homocysteine disturbs the BRB function via activation of NMDAr receptor in HRECs. Targeting NMDAr may propose new therapeutic avenue for patients with DR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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