Two phases of increased cell death in the inner retina following early elimination of the ganglion cell population

Neurons in the inner nuclear layer (INL) of the vertebrate retina undergo c onsiderable programmed cell death during development, but the determinants of this cell death remain largely unknown. The present study examines the r ole of retinal ganglion cells in support of INL neurons in the developing f erret retina. The retinal ganglion cell population was eliminated by optic nerve transection at postnatal day (P) 2, and the incidence of cell death w as examined using terminal deoxytransferase dUTP nick-end labelling (TUNEL) at various ages during the first 3 postnatal weeks. Significant increases in TUNEL-positive cells were observed in the neuroblast layer (NBL) as earl y as P3, prior to synapse formation within the inner plexiform layer (IPL), and again in the INL at P22, the normal peak of naturally occurring cell d eath within the ferret's INL. A decrease in TUNEL-positive cells was found in the NBL at P8. These results show three phases of response to the loss o f retinal ganglion cells and suggest that cells in the NBL/INL are normally dependent on retinal ganglion cells for their survival. Recent studies hav e shown that certain populations of retinal neurons are reduced in adult an imals that had lost the population of ganglion cells during early developme nt, so the present study also examined when this reduction could first be d etected. The number of parvalbumin-immunoreactive amacrine cells was decrea sed significantly in the NBL of the manipulated eye as early as P8, when we could first label this population, and this difference persisted through a dulthood. The fact that cell death in the NBL has already increased within 24 hours of ganglion cell elimination, coupled with the specificity of this effect on the adult complement of INL cell types, shows that cell-cell int eractions controlling survival are already highly specific for particular t ypes of retinal neuron early in development. (C) 2001 Wiley-Liss, Inc.