SOD Mimetics in Age-related Macular Degeneration:

Oxidative damage to photoreceptors and the pigmented retinal epithelial cells (RPEs) are strongly implicated in the early development of AMD. The retina is particularly susceptible to the generation of reactive oxygen species and oxidative stress because of its high consumption of oxygen, high proportion of polyunsaturated fatty acids, and continuous exposure to radiation (light).

The role of superoxide and its control by endogenous SOD is demonstrated by the development of clinical features of AMD in animals where SOD has been compromised. Ribozyme "knock-down" of MnSOD (SOD2) in mice leads to reduced MnSOD protein levels and increased markers of oxidative damage in RPE cells and the choroid. This model leads to a loss of electroretinography response, degeneration of the RPE, thickening of Bruch's membrane, photoreceptor dysfunction, increased auto fluorescence, and elevated levels of A2E and iso-A2E (bis retenoids in lipofuscin), all features of clinical AMD (Justilien et al., Invest Ophthalmol Vis Sci 2007).

Preclinical studies with Inotek SODm compounds support their potential use in AMD, and additional preclinical work is ongoing.