The Spatial Order of Horizontal Cells Is Not Affected by Massive Alterations in the Organization of Other Retinal Cells

Abstract

To test whether retinal mosaics develop through interactions that are restricted primarily to the mosaic cells, we studied the horizontal cell mosaic in mutant mice (rd/rd and rd/bcl2) displaying severe retinal abnormalities. These mutants show that the horizontal cell mosaic develops normally even if these cells lack part of their synaptic input, have anomalous morphologies, eventually decrease in number, and reside in an abnormally packed retinal layer. These data strongly support a developmental design in which the final position of each cell in a retinal mosaic is controlled by interactions between homotypic cells and is independent of other cell types. The present analysis is also an investigation of the effects of photoreceptor degeneration on the horizontal cells in an established animal model of retinitis pigmentosa, the rd/rd mouse. We find that the organization of the horizontal cell mosaic resists photoreceptor degeneration and, furthermore, that bcl2 overexpression prevents the partial loss of horizontal cells secondary to photoreceptor loss. Secondary degeneration hampers attempts to restore retinal function by transplanting photoreceptors or promoting their survival. The anti-apoptotic gene bcl2 appears to be a promising tool to rescue inner retinal neurons, increasing the probability that photoreceptor rescue or substitution may be beneficial to subjects suffering from retinal degenerative diseases.