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Mei Chen, Sofia Pavlou, Ronan Cunning, Heping Xu; Attenuating diabetic vascular degeneration by targeting the P2X7 receptor. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2713. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal vascular degeneration and neurodegeneration are important pathological features of diabetic retinopathy. P2X7 receptor belongs to the purinergic receptor family and is expressed by retinal amacrine cells and photoreceptor cells. Nucleoside reverse transcriptase inhibitors are known to protect retinal pigment epithelia from adenosine triphosphate (ATP)-induced cell damage through P2X7 receptors. We hypothesise that retinal neuronal dysfunction plays an important role in diabetic vasculopathy and diabetic vascular degeneration can be attenuated through the protection of retinal neuronal cells via p2x7 receptor.
Diabetes was induced in C57BL/6J mice by multiple STZ i.p. injection. One month after the onset of diabetes, mice were treated with Lamivudine (once daily, p.o.) . Retinal function was examined by electroretinography (ERG) at 2 month and 6 month after diabetes. Acelluar capillaries were measured from post-mortem eyes of 6 month diabetes mice. In vitro cultured photoreceptor cells (6661W) were treated with ATP and the protective role of Lamivudine (3TC) was measured using YO-Pro-1 uptaking assay.
The expression of P2X7 mRNA was increased in diabetic retina as early as one month after diabetic induction. Lamivudine treatment improved both a-wave and b-wave amplitude in diabetic mice in the ERG analysis. In unison with the improved retinal function, diabetic vascular degeneration was attenuated with less acelluar capillaries in the Lamivudine treated mice compared to vehicle controls (p<0.05). Lamivudine protected photoreceptor from ATP-induced cell death in vitro.
Our study suggested that diabetic vasculopathy can be attenuated through protecting retinal neurons.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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