Cone photoreceptor regeneration in adult fish retina: phenotypic determination and mosaic pattern formation

Abstract

The retina of anamniotes (fish and amphibia), unlike the CNS of most vertebrates, can regenerate neurons following injury. Using the highly ordered mosaic of single and double cones in the retina of the adult green 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 retina. The wound was filled in two ways: a proliferative regeneration of new retina and a nonproliferative movement of the wound boundaries toward the center of the lesion. The nonproliferative movement stretched the surrounding, intact retina. In stretched retina the basic pattern of the cone mosaic was maintained, but it was augmented by new cones, even though cones are not normally generated in intact central retina. The stretch itself likely triggered the anomalous cone production. The new and preexisting cones in stretched retina had their morphological phenotypes influenced by mutual contact, often resulting in atypical morphologies (triple and quadruple cones). In the center of the lesioned area, the regenerated cone mosaic was disordered, had a higher than normal cone density, and contained atypical morphologies. The presence of outer segments and synaptic pedicles suggested that the new cones in regenerated and stretched retina were functional. We interpret these results to mean (1) a stretch-induced decrease in cell density can trigger a compensatory, adaptive neurogenesis, (2) cone morphological phenotypes in fish retina are plastic throughout life, and are influenced by cone-cone contacts, (3) the mechanisms that spatially regulate cone production during normal growth are disrupted regeneration.

Photoreceptor Differentiation during Retinal Development, Growth, and Regeneration in a Metamorphic Vertebrate

“…Regeneration of postmetamorphic dorsal retina was induced using a mechanical lesion paradigm described previously (Hitchcock et al, 1992;Cameron and Easter, 1995). The absolute and relative positions of rod and cone photoreceptors in adult retinas were referenced to two neurogenic structures (Fig.…”

Neurogenesis in the Fish Retina

“…Surgical Injury-The original methods of Lombardo have been modified and applied to several teleosts, including goldfish , sunfish (Cameron and Easter, 1995), and zebrafish (Cameron, 2000). Generally, rather small portions (1-2 mm 2 ) of adult retina are removed, using a transscleral approach, with the flap of sclera sutured back into place in the case of larger lesions.…”

Regeneration of Inner Retinal Neurons after Intravitreal Injection of Ouabain in Zebrafish

“…Models to examine the extent and mechanisms involved in retinal regeneration have been developed using chick, goldfish, and zebrafish (Maier and Wolburg, 1979;Raymond et al, 1988;Fischer et al, 1998;Vihtelic and Hyde, 2000). In teleosts, the retinal neurons regenerated in response to surgical removal of retinal cells (Hitchcock et al, 1992;Cameron and Easter, 1995;Cameron and Carney, 2000), light-or laser-induced photoreceptor degeneration (Braisted et al, 1994;Vihtelic and Hyde, 2000;Wu et al, 2001;Vihtelic et al, 2006), toxin injection (Maier and Wolburg, 1979;Raymond et al, 1988;Negishi et al, 1991a,b;Braisted and Raymond, 1992), or retinal puncture (Fausett and Goldman, 2006). In all of these damage paradigms, INL cells were the source of the regenerated neurons.…”