Abstract
Purpose :
Vision decline is associated with aging in the human retina. However, the mechanisms responsible for retinal function loss during aging are not clear. Here, to improve our knowledge in this field, we proposed to establish whether the eye of the vervet monkey (Chlorocebus sabaeus) is a relevant model. Indeed, the human and vervet eyes are very similar.
Methods :
Immunofluorescent stainings were carried out on histological sections of central and peripheral retinal regions (20 μm), in 3 young (~4-year-old) and 3 old vervet monkeys (~15-year-old). Retinal crossections and flat-mounts were stained for calbindin and PKCα to visualize photoreceptor and rod bipolar cells respectively. The dapi nuclear marker was used to observe retinal cell layers. For PKCα-positive bipolar cells, cell surface and cell circularity were evaluated using the ImageJ software (NIH). Glial fibrillary acid protein (GFAP) allowed to follow Müller cell gliosis.
Results :
Dapi staining revealed striking photoreceptor nucleus misalignment in old retinae compared with young monkeys. Retinal flatmounts stained for calbindin showed a decrease in the density of cone photoreceptors at 15 years. PKCα-positive bipolar cell bodies were much bigger in old retinae (108.2±35.99 mm2, mean ± SD, n=406 cells) than in young primates (46.32±8.4 mm2, mean ± SD, n=525 cells). The shape of bipolar cells was also markedly different between the two age groups, as reflected by the circularity index that was 0.70±0.11 in old and 0.88±0.05 in young monkeys. PKCα-positive bipolar cell sprouting was observed in the outer plexiform layer of 1 old monkey. In the two other monkeys of this group, varicosities appeared in the terminals of bipolar cells, suggesting synaptic rearrangement between bipolar and photoreceptor cells. In addition, GFAP was upregulated in the radial extensions of isolated and clustered Müller cells in old but not in young retinal crossections, indicating that gliosis occurs in aged animals.
Conclusions :
Our results revealed major histological changes in the aging vervet retina, similar to those previously described in the human retina. A possible scenario may be that age-induced photoreceptor cell loss triggers plastic synaptic remodelling in the outer plexiform layer and bipolar cell hypertrophy in order to maintain vision.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.