ONCOGENE EXPRESSION IN RETINAL HORIZONTAL CELLS OF TRANSGENIC MICE RESULTS IN A CASCADE OF NEURODEGENERATION

The phenylethanolamine N-methyltransferase promoter directs the expres sion of the SV40 T antigen to subsets of amacrine and horizontal neuro ns of the retina in a line of transgenic mice. T antigen expression be gins in these cells during the first postnatal week. The horizontal ce lls appear to develop normally for another week but then begin to die. Subsequently, most of the horizontal cells disappear from the central and mid retina, resulting in loss of the outer plexiform layer and ab sence of ribbon synapses between the photoreceptors and bipolar cells. Neuronal transformation occurs only in the peripheral retina. These e xperiments indicate that horizontal neurons are heterogeneous with res pect to susceptibility to transformation and that T antigen expression in a subset of horizontal neurons can be a direct cause of neuronal c ell death. Furthermore, critical interdependencies exist between horiz ontal neurons after retinal neurogenesis is complete.