Decline in constitutive proliferative activity in the zebrafish retina with ageing

It is largely assumed that the fish retina shows continuous and active proliferative and neurogenic activity throughout life. This is based on studies in teleost models. However, work in lampreys and cartilaginous fishes has shown that proliferative and mitotic activity is almost absent in adult individuals of these ancient fish groups. Interestingly, when deepening in the teleost literature one finds that claims of a highly active and continuous proliferation in the adult retina are based on studies in which proliferation was not quantified in a comparative way at different life stages or was mainly studied in juveniles/young adults. Here, we performed a systematic and comparative study of the constitutive proliferative activity of the retina from early developing (2 days post-fertilization) to aged (up to 3-4 years post-fertilization) zebrafish. Cell proliferation was analysed by using immunofluorescence against pH3 (marker of mitotic cells) and PCNA (marker of proliferating cells). We observed a decline in cell proliferation in the whole retina with ageing, even despite the occurrence of a wave of secondary proliferation during sexual maturation. Interestingly, during this wave of secondary proliferation the distribution of proliferating and mitotic cells changes from the inner to the outer nuclear layer in the central retina. Importantly, in aged zebrafish there is a virtual disappearance of mitotic activity. Our results showing a decline in proliferative activity of the zebrafish retina with ageing are of crucial importance since it is largely assumed that the fish retina grows continuously throughout life from progenitor cells located in the periphery.