Cones Regenerate from Retinal Stem Cells Sequestered in the Inner Nuclear Layer of Adult Goldfish Retina

• Published in: Investigative ophthalmology & visual science Vol. 42; no. 9; pp. 2115 - 2124
• Main Authors: Wu, David M, Schneiderman, Todd, Burgett, Jason, Gokhale, Parag, Barthel, Linda, Raymond, Pamela A
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.08.2001; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Biological and medical sciences; Bromodeoxyuridine - metabolism; Cell Differentiation; Cell Division; Eye and associated structures. Visual pathways and centers. Vision; Fluorescent Antibody Technique, Indirect; Fundamental and applied biological sciences. Psychology; Goldfish - physiology; Immunoenzyme Techniques; In Situ Hybridization; Laser Therapy; Microglia - physiology; Regeneration - physiology; Retina - cytology; Retina - surgery; Retinal Cone Photoreceptor Cells - cytology; Retinal Cone Photoreceptor Cells - physiology; Retinal Rod Photoreceptor Cells - physiology; Stem Cells - cytology; Stem Cells - physiology; Vertebrates: nervous system and sense organs; Human; Cone; Stem cell; Photoreceptor; Retina; Muller cell; Ablation; Visual system; Regeneration; Vertebrata; Animal; Pisces; Laser; Adult; Physiology
• ISSN: 0146-0404; 1552-5783

To determine whether retinal progenitor cells in the inner nuclear layer give rise to regenerated cones after laser ablation of photoreceptors in adult goldfish retina. Using a technique developed previously in this laboratory, photoreceptors in the retina of adult goldfish were ablated with an argon laser. The mitotic marker, bromodeoxyuridine, was used to label proliferating and regenerated cells, which were identified with cell-specific markers. Cells proliferating locally within lesion included microglia, Müller glia, and retinal progenitors in the inner nuclear layer (INL). The nuclei of both Müller glia and associated retinal progenitors migrated from the inner to the outer nuclear layer. The proliferating retinal progenitors, which express Notch-3 and N-cadherin, regenerated cone photoreceptors and then rod photoreceptors. Previous work has demonstrated that photoreceptors in the goldfish retina regenerate selectively after laser ablation, but the source of regenerated cones has not been identified. The results reported here provide support for the existence of retinal stem cells within the adult fish retina that are capable of regenerating cone photoreceptors. The data also support the involvement of Müller glia in the production of regenerated cones.