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

Clin Ophthalmol. 2008 Dec;2(4):801-16. doi: 10.2147/opth.s3967.


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.

Keywords: Müller cells; amyloid-β; blood-retinal barrier.