Glial and endothelial blood-retinal barrier responses to amyloid-beta in the neural retina of the rat

大鼠神经视网膜中胶质细胞和内皮细胞血视网膜屏障对淀粉样蛋白-β的反应

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作者:Peter Jb Anderson, Hr Watts, Cj Hille, Kl Philpott, P Clark, M Croucher S Gentleman, Ling-Sun Jen

Abstract

The effects of an intravitreal or subretinal injection of soluble or aggregated forms of Abeta(1-42) on retinal nestin-immunoreactivity (-IR) and glial fibrillary acidic protein (GFAP)-IR in astrocytes and Müller glial cells and the integrity of the blood-retinal barrier (BRB) were tested in the in vivo rat vitreal-retinal model. Retinas were exposed for 1, 2, 3, 5 or 30 days. We present novel data demonstrating that aggregated Abeta(1-42) up-regulates nestin-IR in astrocytes and Müller cells, with a graded response directly related to the length of pre-injection aggregation time. Similar results were obtained with GFAP-IR, but the signal was weaker. An intravitreal injection of aggregated Abeta(1-42) led to VEGF-IR up-regulation, particularly in the GCL and to a lesser extent in the INL. VEGFR1-IR (Flt1) was also increased, particularly in Müller cells and this was accompanied by marked leakage of albumin into the retinal parenchyma of the injected eye, but not in the contralateral eye.

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