CONE PHOTORECEPTOR REGENERATION IN ADULT FISH RETINA - PHENOTYPIC DETERMINATION AND MOSAIC PATTERN-FORMATION

The retina of anamniotes (fish and amphibia), unlike the CNS of most v ertebrates, can regenerate neurons following injury. Using the highly ordered mosaic of single and double cones in the retina of the adult g reen sunfish (Lepomis cyanellus) as our model system, we examined the events that followed the surgical excision of a small patch of central retina. After surgery there was a transient elevation in the number, and a change in the distribution, of proliferative cells within the re tina. The wound was filled in two ways: a proliferative regeneration o f new retina and a nonproliferative movement of the wound boundaries t oward the center of the lesion. The nonproliferative movement stretche d the surrounding, intact retina. In stretched retina the basic patter n of the cone mosaic was maintained, but it was augmented by new cones , even though cones are not normally generated in intact central retin a. The stretch itself likely triggered the anomalous cone production. The new and preexisting cones in stretched retina had their morphologi cal phenotypes influenced by mutual contact, often resulting in atypic al morphologies (triple and quadruple cones). In the center of the les ioned area, the regenerated cone mosaic was disordered, had a higher t han normal cone density, and contained atypical morphologies. The pres ence of outer segments and synaptic pedicles suggested that the new co nes in regenerated and stretched retina were functional. We interpret these results to mean (1) a stretch-induced decrease in cell density c an trigger a compensatory, adaptive neurogenesis, (2) cone morphologic al phenotypes in fish retina are plastic throughout life, and are infl uenced by cone-cone contacts, (3) the mechanisms that spatially regula te cone production during normal growth are disrupted during regenerat ion.