Localization of 4-hydroxy 2-nonenal immunoreactivity in aging human retinal Muller cells

Abstract

Muller cells play a pivotal role in maintaining retinal homeostasis of the extracellular fluid environment. Information on whether human retinal Muller cells suffer from oxidative stress with normal aging is lacking. We examined post mortem human retinas for the localization of a biomarker of lipid peroxidation (4-hydroxy -nonenal, 4-HNE) by immunohistochemistry. We procured human eyes from donors (N =11 ; age: 45-9 years; post mortem delay:1-3 h), who had no history of ocular diseases. They were fixed in 4% paraformaldehyde; the retinas cryosectioned; labeled against anti-4-HNE employing the immunoperoxidase method. Compared to the lower age group (45-56 years), in the advanced age group (67-9 years), immunoreactivity (IR) to 4-HNE was prominent in peripheral Muller cell end-feet, select cells in the inner nuclear layer; in outer fibers located in the macular fiber layer of Henle. Colocalization with glutamine synthetase revealed that the 4-HNE positive profiles in the inner nuclear layer were Muller cells. Quantitative analysis revealed that the percentage of immunopositive cells in the inner nuclear layer as well as the grey levels of the immunoreaction products in the parafoveal; peripheral retinal regions significantly increased in the advanced age group. The findings indicate that Muller cells of human retina suffer from lipid peroxidation; are susceptible to damage in the course of normal, advanced aging.