Müller cell vulnerability in aging human retina: Implications on photoreceptor cell survival

Müller glial cells (MC) support various metabolic functions of the retinal neurons, and maintain the homeostasis. Oxidative stress is intensified with aging, and in human retina, MC and photoreceptors undergo lipid peroxidation and protein nitration. Information on how MC respond to oxidative stress is vital to understand the fate of aging retinal neurons. This study examined age-related changes in MC of donor human retina (age: 35-98 years; N = 18 donors). Ultrastructural and immunohistochemical observations indicate that MC undergo gliosis and increased lipid peroxidation, and show osmotic changes with advanced aging (>80 years). Photoreceptor cells also undergo oxidative-nitrosative stress with aging, and their synapses also show clear osmotic swelling. MC respond to oxidative stress via proliferation of smooth endoplasmic reticulum in their processes, and increased expression of aquaporin-4 in endfeet and outer retina. In advanced aged retinas (81-98 years), they showed mitochondrial disorganisation, accumulation of lipids and autophagosomes, lipofuscin granules and axonal remnants in phagolysosomes in their inner processes, suggesting a reduced phagocytotic potential in them with aging. Glutamine synthetase expression does not alter until advanced aging, when the retinas show its increased expression in endfeet and Henle fiber layer. It is evident that MC are vulnerable with normal aging and this could be a reason for photoreceptor cell abnormalities reported with aging of the human retina.