The metabolite receptor SUCNR1 in oxidative stress-induced age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of vision impairment in elderly people. AMD is a multifactorial disease which is characterised by complex interactions between metabolic and environmental factors as well as multiple genetic susceptibility factors. The exact mechanism of the most prominent environmental factors, age and smoking, in combination with genetic susceptibility factors is little studied. Here, we set out to study the influence of age, smoking induced oxidative stress and the role of succinate receptor 1 (SUCNR1) in AMD development in mice. Sucnr1 wild-type (WT), heterozygous (HT) and knock-out (KO) mice were exposed to smoking related oxidative stress by the addition of hydroquinone (HQ), the most abundant oxidant in cigarette smoke, to the drinking water of the mice. Using immunohistochemical staining, accumulation of oxidized LDL (oxLDL) in the mouse retina was assessed at 40 and 48 weeks of age. At 40 weeks of age, a significant increase in oxLDL in the Sucnr1 KO mice treated with HQ was observed when compared to the WT and HT mice treated with HQ (p<0.01). However, at 48 weeks, no significant difference was observed between any of the groups. A second experiment analyzing the mice at 40 weeks of age was unable to confirm the observed results of the first experiment. We identified oxLDL accumulations in Sucnr1 KO retinas exposed to HQ, but were unable to repeat this finding. Therefore, under the present conditions, the Sucnr1 KO mouse model is not a suitable model to study AMD development.