Evaluating the effect of photoperiod modulation and melatonin on regenerative ability of lead acetate induced retinal degeneration in zebrafish

Abstract

Retinal degenerative disorders are prevalent globally. The changes in physiology and exposure to environmental components enhance the risk of these disorders in addition to genetic changes. Various animal models have been developed to understand the etiology behind these disorders and to develop a therapeutic intervention to treat these disorders. However to illustrate the impact of hazardous chemicals on retina are not well explored. Therefore in this study, a retinal degenerative model was prepared using environmental toxicant i.e. lead acetate (PbAc). Zebrafish was approached as an animal model in this study as it has the capability to regenerate its retina upon damage. Melatonin a neurohormone plays a part in providing maintenance of neuronal cells in a circadian manner. However its role in neuronal cell regeneration is not well established. Thus in order to investigate the impact of melatonin on retinal cell regeneration, different photoperiods (regular photoperiod, constant light, constant dark) and exogenous melatonin were given to PbAc induced retinal degenerative model of zebrafish for 10 and 30 days. Behavioral, histopathological and molecular changes were analyzed post exposure to different photoperiods and exogenous melatonin. Behavioral study showed the restoration of vision and reduction in stress in retinal degenerative model post exposure to different photoperiods and exogenous melatonin. 10 days exposure to melatonin and constant dark photoperiod resulted in faster regenerative response than regular photoperiod condition depicting the impact of photoperiod on retinal regeneration. After 30 days exposure, constant light group also showed regeneration of photoreceptor but with alteration in morphology. Ultrastructural and immunohistochemical study corresponded with light microscopic study as it show the presence of Muller glia cell that play primary role in retinal regeneration. Molecular study outlined the expression of genes involved in retinal regeneration post exposure to melatoninandconstantdark