Hernández Núñez, IsmaelQuelle Regaldie, AnaSánchez Piñón, LauraAdrio Fondevila, FátimaCandal Suárez, Eva MaríaBarreiro Iglesias, Antón2024-01-242024-01-242021Hernández-Núñez, I.; Quelle-Regaldie, A.; Sánchez, L.; Adrio, F.; Candal, E.; Barreiro-Iglesias, A. Decline in Constitutive Proliferative Activity in the Zebrafish Retina with Ageing. Int. J. Mol. Sci. 2021, 22, 117151422-0067http://hdl.handle.net/10347/31976Supplementary Materials The following are available online at https://www.mdpi.com/article/10.3390/ijms222111715/s1. Table S1: Studies demonstrating the presence of proliferating cells in the juvenile/adult retina of different teleost species. File S1: Mean ± S.E.M. data and data on statistical multiple comparisons related to graphs shown in Figure 2; File S2: Mean ± S.E.M. data and data on statistical multiple comparisons related to graphs shown in Figure 3.It is largely assumed that the teleost retina shows continuous and active proliferative and neurogenic activity throughout life. However, when delving into the teleost literature, one finds that assumptions about 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 the 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-fertilisation) to aged (up to 3–4 years post-fertilisation) zebrafish. The mitotic activity and cell cycle progression were analysed by using immunofluorescence against pH3 and PCNA, respectively. We observed a decline in the cell proliferation in the retina with ageing despite the occurrence of a wave of secondary proliferation during sexual maturation. 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 the proliferative activity of the zebrafish retina with ageing are of crucial importance since it is generally assumed that the fish retina has continuous proliferative activity throughout life.eng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY)http://creativecommons.org/licenses/by-nc-sa/4.0/RetinaZebrafishProliferationSecondary neurogenesisPCNApH3AgeingDecline in Constitutive Proliferative Activity in the Zebrafish Retina with Ageingjournal article10.3390/ijms222111715open access