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

The effects of an intravitreal or subretinal injection of soluble or aggregated forms of Aβ1–42 on retinal nestin-immunoreactivity (−IR) and glial fibrillary acidic protein (GFAP)-IR in astrocytes and Muller 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 Aβ1–42 up-regulates nestin-IR in astrocytes and Muller 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 Aβ1–42 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 Muller cells and this was accompanied by marked leakage of albumin into the retinal parenchyma of the injected eye, but not in the contralateral eye.