Numbers of Neurons in the Retinal Ganglion Cell Layer of the Rat Do Not Change throughout Life

Abstract

Background: There have been many assumptions made about neuronal loss in mammals due to aging. However, when we examined the retinal ganglion cell layer of a marsupial, the quokka, from 0.5 to 13.5 years of age, we found that the total neuron number did not decrease significantly even into extreme old age. The retinal area increased slowly throughout life, leading to a decrease in cell density. Neuronal death in the rat retina has been assumed, since the cell density has been seen to fall with age. However, a similar study to ours in the quokka has never been performed in the laboratory rat, the model for so many experimental investigations. Objective: We decided to test the hypothesis that rats do not lose neurons due to aging and that an increase in retinal area, and not cell death, as previously suggested, might underlie the decreasing cell density seen in aging animals such as rats. Methods: We kept laboratory rats under standard, unvarying conditions throughout the trial, sacrificing 3 animals every 3 months up to 30 months, and examined the retinal ganglion cell layer through adult life. Results: We found that the numbers of neurons did not decrease in this species, even in the oldest rats. We also saw that the retinal area increased slowly with a concomitant slow decrease in mean neuronal density. Soma diameters of neurons gradually increased throughout life. Conclusions: When rats are kept under standard conditions, there is no neuronal loss in the retina during aging, although the cell density does decrease as a result of retinal expansion. It is not sufficient to measure retinal cell density to determine cell loss. In addition, it is important to know that in normal conditions there is no cell loss in the retinal ganglion cell layer as a result of aging. Any loss that is seen must be a result of additional factors.

No age-related cell loss in three retinal nuclear layers of the Long-Evans rat

“…Our results are consistent with those studies in which the total number of retinal ganglion cells was estimated Kim et al, 1996;Harman & Moore, 1999;Harman et al, 2003! but against other studies in which the cell density~per unit area! Our results are consistent with those studies in which the total number of retinal ganglion cells was estimated Kim et al, 1996;Harman & Moore, 1999;Harman et al, 2003! but against other studies in which the cell density~per unit area!…”

“…was used for comparisons between age groups~Cano et al, 1986; Gao & Hollyfield, 1992;Weisse, 1995;Cavallotti et al, 2001!. and previous studies Cano et al, 1986;Weisse, 1995;Cavallotti et al, 2001;Harman et al, 2003! proved that the thickness of the retina significantly decreased whereas the area of the entire retina increased during the aging process. Evidence from this study~Table 1!…”

“…Such alteration may extend to retinal cells that are derived from the embryonic diencephalon~Yuan & Yankner, 2000!. Expansion and thinning of the retina during aging have been documented in the rat~Cano et Weisse, 1995;Harman et al, 2003!. It was also found that the total number of retinal ganglion cells was unaffected by aging in the rat Harman et al, 2003!, quokka~Harman & Moore, 1999!, rhesus monkey~Kim et al, 1996, and very few apoptotic cells were observed in the retina of the aging human~Dunaief et al, 2002!. significantly declines during life, being the primary basis for the above assumption.…”

Connexin 30 Expression and Frequency of Connexin Heterogeneity in Astrocyte Gap Junction Plaques Increase with Age in the Rat Retina

“…We have previously shown that astrocytes lose their ability to proliferate after 9 months, equivalent to a young adult in humans, and that the frequency of apoptosis increases significantly and persistently into old age [21]. In contrast, retinal ganglion cell numbers have been shown to remain constant in the rat retina with age [22]. Thus during aging a lower astrocyte to neuronal ratio results, placing an increased demand on the remaining astrocytes to maintain retinal homeostasis [21].…”

Microarray-based gene expression analysis during retinal maturation of albino rats

“…However, despite the widespread use of the rat in retinal research, there are only a few studies of retinal age-related molecular and morphological changes covering the first 6 months of life. Although a few histological analyses of the rat retina were reported, including a morphometric study in the first 2 weeks of life [11] and RGC count in 3 and 6 month-old rats [12], we are aware of only one study in which a sequential analysis of the rat retina between weaning and adulthood was performed [13].…”