Aging is a biological phenomenon that involves an increase of oxidative stress associated with gradual degradation of the structure and function of the optic nerve. Gender differences and subsequent deterioration of optic nerve are an interesting topic, especially because there is little published work concerning it. One hundred male and female Wistar albino rats' with ages 1, 6, 18, 24, and 30 months (n = 20 equal for male and female) were used. At the time interval, optic nerve was investigated by light and transmission electron microscopy (TEM), assessments of antioxidant enzymes (catalase, superoxide dismustase, and glutathione-S-transferase), caspase 3 and 7, malondialdhyde, flow cytometry of DNA, annexin v, and CD8, immunochemistry of vascular endothelial growth factor (VEGF), CD31, and CD45, and single-strand DNA fragmentation. Light and TEM observations of the older specimens (24 and 30 months) revealed apparent deterioration of optic nerve axons, abundant oligodendrocytes with pyknotic nuclei, swollen astrocytes, angiogenesis, vacuolar degeneration, and mitochondrial damage. Females were highly susceptible to aging processes. Concomitantly, there was a marked reduction of antioxidant's enzymes and an increase of lipid peroxidation and apoptotic markers. Old age exhibited a marked increase of G1 apoptosis, UR and LR of annexin V and CD8 as well as increased immuno-positive reaction with VEGR, CD31 and CD45. We conclude that aging contributed to an increase of oxidative stress resulting from damage of mitochondria in axons, oligodendrocytes, and astrocytes. Age-related loss of optic nerve axons is associated with multifactorial agents including reduction in antioxidant enzymes, disruption of vasculature, astrocyte, and oligodendrocyte, demyelination, and damage of mitochondria, which enhance the liberation of reactive oxygen species as assessed by an increase of apoptotic markers malondialdhyde and caspase 3 and 7.
