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

Müller cells play a pivotal role in maintaining retinal homeostasis of the extracellular fluid environment. Information on whether human retinal Müller 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 2-nonenal, 4-HNE) by immunohistochemistry. We procured human eyes from donors (N=11; age: 45-91 years; post mortem delay: 1-3h), who had no history of ocular diseases. They were fixed in 4% paraformaldehyde and the retinas cryosectioned and labeled against anti-4-HNE employing the immunoperoxidase method. Compared to the lower age group (45-56 years), in the advanced age group (67-91 years), immunoreactivity (IR) to 4-HNE was prominent in peripheral Müller cell end-feet, select cells in the inner nuclear layer and 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 Müller 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 and peripheral retinal regions significantly increased in the advanced age group. The findings indicate that Müller cells of human retina suffer from lipid peroxidation and are susceptible to damage in the course of normal, advanced aging.