Selective regeneration of photoreceptors in goldfish retina

Previous work has shown that the neural retina in adult goldfish can regenerate. Following retinal damage elicited by surgical or cytotoxic lesions, missing neurons are replaced by foci of proliferating neuroepithelial cells, which previous studies have suggested are derived from rod precursors. In the intact retina, rod precursors proliferate but produce only new rods. The regenerative responses observed previously have involved replacement of neurons in all retinal layers; selective regeneration of specific neuronal types (except for rod photoreceptors) has not been reported. In the experiments described here, we specifically destroyed either cones alone or cones and rods with an argon laser, and we found that both types of photoreceptors regenerated within a few weeks. The amount of cone regeneration varied in proportion to the degree of rod loss. This is the first demonstration of selective regeneration of a specific class of neuron (i.e., cones) in a region of central nervous tissue where developmental production of that class of neuron has ceased. Selective regeneration may be limited to photoreceptors, however, because when dopaminergic neurons in the inner retina were ablated with intraocular injections of 6-hydroxydopamine, in combination with laser lesions that destroyed photoreceptors, the dopaminergic neurons did not regenerate, but the photoreceptors did. These data support previous studies which showed that substantial cell loss is required to trigger regeneration of inner retinal neurons, including dopaminergic neurons. New observations here bring into question the presumption that rod precursors are the only source of neuronal progenitors during the regenerative response. Finally, a model is presented which suggests a possible mechanism for regulating the phenotypic fate of retinal progenitor cells during retinal regeneration.