Abstract
Purpose: :
To examine the protective effect of donepezil, an acetylcholinesterase inhibitor which was developed as a therapeutic agent for Alzheimer’s disease, on axotomized rat retinal ganglion cells (RGCs) in vivo.
Methods: :
Left optic nerve (ON) was axotomized about 2 mm to the posterior eye pole in adult female Dark–Agouti (DA) rats. RGCs were retrogradely labeled with fluorescent tracer hydroxystillbamidine applied to the axotomized ON stump. Donepezil (5mg/kg), dissolved in distilled water, was administered orally twice daily for six days. In control animals, same volume of distilled water was administered in the same manner. Seven days after axotomy, the density of viable RGCs was determined by counting the number of tracer–labeled RGCs in flat–mounted retinas.
Results: :
At seven days after ON axotomy, the mean density of viable RGCs (cell number per square millimeter) was 1135 ± 69 (average ± SD, n=7). Oral administration of donepezil significantly increased the number of viable RGCs (1330 ± 66, n=6). Oral administration of vehicle alone did not affect the survival of RGCs (1075 ± 122, n=6).
Conclusions: :
Oral administration of donepezil prevented axotomy–induced rat RGC death.
Keywords: neuroprotection • apoptosis/cell death • retina: proximal (bipolar, amacrine, and ganglion cells)