Imbalance of homeostasis causes permanent changes in the body with time. The central nervous system is especially prone to these changes since it possesses limited regenerative capacity. In the retina, neurons are damaged during the aging process, and this eventually leads to deterioration of vision. In our 2-year-long study, we examined genetically closely related rat individuals to disclose the hidden retinal causes of age-associated visual dysfunction. Morphometric analysis showed significant reduction of the retina thickness with aging, particularly that of the inner plexiform layer. To reveal changes between the age groups, we used immunohistochemistry against vesicular glutamate transporter 1 protein for photoreceptor and bipolar cell terminals, Brn3a for ganglion cells, calbindin 28 kDa for horizontal cells, parvalbumin for AII amacrines, protein kinase Cα for rod bipolar cells, tyrosine hydroxylase for dopaminergic cells, glial fibrillary acidic protein for glial cells, and peanut-agglutinin labeling for cones. The most significant decrease was observed in the density of photoreceptor and the ganglion cells in the aging process. By using immunocytochemistry and western blot technique, we observed that calbindin and vesicular glutamate transporter 1 protein staining do not change much with aging; tyrosine hydroxylase, parvalbumin and calretinin showed the highest immunoreactivity during the midlife period. Most interestingly, the level of glial fibrillary acidic protein also changes similarly to the previously named markers. Our results provide further evidence that protein content is modified at least in some cell populations of the rat retina, and the number of retinal cells declined with aging. We conclude that senescence alone may cause structural and functional damage in the retinal tissue.