Birth and fate of proliferative cells in the inner nuclear layer of the mature fish retina

Abstract

In teleost fish, unlike other vertebrates, the retina continues to grow throughout the animal's life both by stretching of the mature tissue and by the addition of new cells. Following larval development, new retinal cell birth is known to occur in a rim at the periphery of the mature retina and in the outer nuclear layer (ONL). We have now found that cell birth and proliferation also occurs in the inner nuclear layer (INL) of the mature fish retina. In rainbow trout (Onchoryncus mykiss), proliferative cells exist in the INL of fish of all ages, at least up to 2 years posthatching. The proliferative cells form clusters in the INL that align in radial columns, reaching from the inner to the outer plexiform layers. The density of proliferative cell clusters changes along the equatorial plane of the retina and is highest near both the nasal and temporal poles. Our data suggest that, after birth, the proliferative cells migrate away from the INL and into the ONL, with a half-time of about 3 days, and their cell bodies can be seen in the outer plexiform layer. Once they are in the ONL, the proliferative cells continue to divide and likely give rise to the precursor cells that differentiate into new rod photoreceptors.

Quantitative evaluation of the distribution of proliferating cells in the adult retina in three cyprinid species

“…Our results, indicating the existence of dividing cells in the INL in normal adult fish retina, support the hypothesis of the persistence of these quiescent cells with capacity to proliferate in response to specific cues. In uninjured retina, dividing cells in the INL, with similar characteristics to those observed in regeneration, have been seen in juvenile goldfish (Johns 1982;Otteson et al 2001), after the intraocular injection of growth factors in goldfish (Negishi and Shinagawa 1993) and in rainbow trout (Julian et al 1998). A study of deep-sea fish, including chondrichtyes and several species of marine teleost, also mentions proliferating cells in the INL (Fröhlich et al 1995).…”

“…Nevertheless, these cells have not been found in normal adults of some species (Johns 1982;Kim et al 1997). It has been suggested that these cells in the INL proliferate very slowly and, therefore, it is difficult to detect them by transient labels of proliferation such as PCNA or pulse labeling with BrdU (Julian et al 1998;Otteson et al 2001). In the present study, we observed cell proliferation in the INL in adult fish with normal growth rate, by anti-PCNA immunostaining.…”

“…Therefore, PCNA labeling, with the protocol that we used, is suitable for detecting the dividing cells of the INL. Julian et al (1998), in their study of rainbow trout, demonstrated that proliferating cells in the INL migrate toward the ONL, where they may give rise to rod precursors. It was proposed, therefore, that in normal conditions these cells are progenitors of the rod precursors (Julian et al 1998;Otteson et al 2001).…”

“…Julian et al (1998), in their study of rainbow trout, demonstrated that proliferating cells in the INL migrate toward the ONL, where they may give rise to rod precursors. It was proposed, therefore, that in normal conditions these cells are progenitors of the rod precursors (Julian et al 1998;Otteson et al 2001). In our study, PCNA + cells in the ONL were often distributed in patches of cells throughout the retina and, frequently, proliferating cells appeared in the INL located just below one of these groups.…”

“…Dividing cells have been detected in the INL of undamaged retinas in juvenile, but not in adult, goldfish (Johns 1982;Otteson et al 2001); therefore it was suggested that they were progenitors of rod precursors that proliferate and migrate into the ONL only in early developmental stages. Nonetheless, proliferation in normal adult retinal INL has been described in rainbow trout, being assumed to be due to a greater adult growth rate or to the use of different labeling methods (Julian et al 1998). …”