Apoptosis during development of the human retina: Relationship to foveal development and retinal synaptogenesis

Apoptosis in the ganglion cell (GCL) and inner nuclear (INL) layers of huma n fetal retinae aged 14-35 weeks of gestation (WG) was investigated in rela tion to synaptogenesis and foveal depression formation. Terminal transferas e dUTP-biotin nick end labeling (TUNEL) was used to identify apoptosis, and synapse development was demonstrated by synaptophysin immunoreactivity (-I R). The distribution of apoptotic cells and synaptophysin-IR was studied as a function of eccentricity. Between 14 and 23-24 WG in the GCL, rates of a poptosis were relatively low in central retina. A shallow fovea was detecte d at 23-24 WG. In the central GCL, the rate of apoptosis was 0.21% of viabl e cells compared with a higher incidence of 0.79-1.64% peripherally. Apopto sis in the INL was 2-8 times greater than that in the GCL. At 14-15 WG, pea k death occurred at the incipient fovea; however, by 20 WG the distribution was bimodal, with peaks at more eccentric locations on either side of the incipient fovea with increasing age. Approximately 90% of INL apoptotic cel ls were in the middle and outer regions, suggesting that bipolar cells form ed the majority of dying neurons. Synaptophysin-IR was present in cones, bi polar cells, and processes in the inner and outer plexiform layers at the i ncipient fovea at 14 WG and spread peripherally with increasing age. The pe ripheral margin of synaptophysin-IR coincided with areas of peak INL apopto sis. This pattern suggests that bipolar cell elimination is associated with the onset of synaptogenesis. Apoptosis in the GCL and INL is not a signifi cant factor in foveal depression morphogenesis. (C) 1999 Wiley-Liss, Inc.