Age related distribution of 4-hydroxy 2-nonenal immunoreactivity in human retina

Abstract

The retina is prone to be damaged by oxidative stress (OS), owing to its constant exposure to light, high rate of oxygen consumption and high membrane lipid content. Lipid peroxidation in aging human retina has been shown by biochemical means. However, information on the cellular sites of OS and antioxidant responses in aging human retina remains limited. Here, we show distribution of immunoreactivity (IR) to a marker of lipid peroxidation (4-hydroxy 2-nonenal [HNE] and antioxidant enzymes involved in counteracting lipid peroxidation (glutathione S-transferase-π1 and glutarexoxin-1) in donor human retinas at different ages (35–91 years; N = 24). Initially, HNE-IR was present in few macular cone outer segments (COS, sixth decade). With aging, IR appeared in many COS and peaked at ninth decade (14 vs 62 per 3850 μm2 area between 6 and 9 decade; p < 0.001) in the parafovea then seen elsewhere (perifoveal, mid-peripheral and nasal). IR was seen in the parafovea of all retinas, whereas it was present in 8/24 of perifoveal and 6/24 of mid-peripheral retinas, indicating that the parafovea is susceptible to undergo lipid peroxidation. Foveolar COS were immunonegative until 81 years, which developed IR later (>83 years). IR to glutathione S-transferase-π1 was moderate until eight decade and then showed a decrease in photoreceptor cells between ninth and tenth decade, while glutaredoxin-1 maintained a steady expression with aging. Damaged COS were present in aged retinas, and inner segments and photoreceptor nuclei also showed some degree of alterations. Although there was increased lipid peroxidation with aging, cone death was minimal in those retinas. The two antioxidant enzymes studied here, may play a role in protecting photoreceptors against OS with advanced aging.