Decline in Constitutive Proliferative Activity in the Zebrafish Retina with Ageing.

Ismael Hernández-Núñez,Antón Barreiro-Iglesias,Fátima Adrio,Eva Candal,Laura Sánchez,Ana Quelle-Regaldie

doi:10.3390/ijms222111715

Abstract

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.

Highlights

The zebrafish retina exhibits the typical morphology and structure of the vertebrate retina, with a ciliary marginal zone (CMZ) located at the retinal margin containing different types of progenitor cells (Figure 1A) and a highly organised central retina (Figure 1A), which can be observed from 2.5 dpf [42], formed by three nuclear layers: the outer nuclear layer (ONL), where the nuclei of photoreceptors are located; the inner nuclear layer (INL), where the nuclei of horizontal, bipolar, amacrine, and Müller glia cells are located; and the ganglion cell layer (GCL), which contains the nuclei of ganglion cells
These cells become connected within two plexiform layers: the outer plexiform layer (OPL) and the inner plexiform layer (IPL)
The 2 to 7 dpf period coincides with early zebrafish development (Figure 1B; the zebrafish has a functional retina at about 3 dpf [43])

Summary

Introduction

The central nervous system (CNS) is formed from a highly active neurogenic neuroepithelium. Proliferative and neurogenic activities are gradually lost in most CNS regions, and, in postnatal life, neurogenic activity is restricted to specific regions called neurogenic niches [1,2]. The presence of postnatal neurogenic activity in the CNS was progressively lost during vertebrate evolution (reviewed in [3,4,5,6,7,8]). Different vertebrate species show different postnatal/adult proliferative and neurogenic rates and different numbers of neurogenic niches in the CNS, which are more abundant in teleost fishes (reviewed in [3,4,5,6,7,8,9])

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Discussion

Conclusion