Cones regenerate from retinal stem cells sequestered in the inner nuclear layer of adult goldfish retina

PURPOSE. To determine whether retinal progenitor cells in the inner nuclear layer give rise to regenerated cones after laser ablation of photoreceptor s in adult goldfish retina. METHODS. Using a technique developed previously in this laboratory, photore ceptors in the retina of adult goldfish were ablated with an argon laser. T he mitotic marker, bromodeoxyuridine, was used to label proliferating and r egenerated cells, which were identified with cell-specific markers. RESULTS. Cells proliferating locally within lesion included microglia, Mull er glia, and retinal progenitors in the inner nuclear layer (INL). The nucl ei of both Muller glia and associated retinal progenitors migrated from the inner to the outer nuclear layer. The proliferating retinal progenitors, w hich express Notch-3 and N-cadherin, regenerated cone photoreceptors and th en rod photoreceptors. CONCLUSIONS. Previous work has demonstrated that photoreceptors in the gold fish retina regenerate selectively after laser ablation, but the source of regenerated cones has not been identified. The results reported here provid e support for the existence of retinal stem cells within the adult fish ret ina that are capable of regenerating cone photoreceptors. The data also sup port the involvement of Muller glia in the production of regenerated cones.