Generation of retinal ganglion cells is modulated by caspase-dependent programmed cell death

Abstract

Programmed cell death occurs during both early and late neural development. The mechanisms for the regulation and execution of the early cell death as well as its developmental role are still not fully understood. In this work we have studied the early programmed cell death in the retinal neuroepithelium. Apoptotic cells were selectively located around the optic nerve head in the retinal neuroepithelium of 2- to 6-day-old chick embryos. TUNEL-positive cells and cells which were immunostained for activated caspase-3 showed overlapping distributions suggesting that caspase-3 is involved in the early retinal cell death. Caspase-3 involvement in early retinal cell death was also demonstrated by in vivo treatment with caspase inhibitors z-DEVD-fmk and Boc-D-fmk. After 6 h of treatment, the number of TUNEL-positive cells was reduced by 50%. Sustained treatments (20 h) resulted in a slight widening in the central part of the neural retina but the retinal ganglion cell axons maintained their organization and navigation towards the optic fissure. The most prominent result after inhibition of cell death was an increase in the number of retinal ganglion cells which also produced an enlargement of the ganglion cell layer and an increased number of ganglion cell axons. In conclusion, our results show that caspase-dependent programmed cell death occurs in the embryonic chick retina and that it plays a role to modulate the generation of retinal ganglion cells.