Capn5 expression in the healthy and regenerating zebrafish retina

Abstract

AbstractPurposeAutosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a devastating inherited autoimmune disease of the eye that displays features commonly seen in other eye diseases, such as retinitis pigmentosa and diabetic retinopathy. ADNIV is caused by a gain of function mutation in Calpain-5 (CAPN5), a calcium dependent cysteine protease. Very little is known about the normal function of Capn5 in the adult retina, and there are conflicting results regarding its role during mammalian embryonic development. The zebrafish (Danio rerio) is an excellent animal model for studying vertebrate development and tissue regeneration, and represents a novel model to explore the function of Capn5 in the eye.MethodsWe characterized the expression of Capn5 in the developing zebrafish central nervous system (CNS) and retina, in the adult zebrafish retina, and in response to photoreceptor degeneration and regeneration using whole mount in situ hybridization, fluorescent in situ hybridization (FISH), and immunohistochemistry.ResultsIn zebrafish, capn5 is strongly expressed in the developing embryonic brain, early optic vesicles, and in newly differentiated retinal photoreceptors. We found that expression of capn5 co-localized with cone specific markers in the adult zebrafish retina. We observed an increase in expression of Capn5 in a zebrafish model of chronic rod photoreceptor degeneration and regeneration. Acute light damage to the zebrafish retina, was accompanied by an increase in expression of Capn5 in the surviving cones and in a subset of Müller glia.ConclusionsThese studies suggest that Capn5 may play a role in CNS development, photoreceptor maintenance, and photoreceptor regeneration.