The Ageing Retina: Structure, function and the effect of 670nm light

Ageing of the retina is the most significant risk factor for age-related macular degeneration (AMD). Photoreceptor decline in ageing and AMD are inferred from morphological and psychophysical changes. Although cumulative insults may be responsible for photoreceptor decline, a key area is the loss of mitochondrial function. Mitochondrial dysfunction can be modulated by exposure to red/ near-infrared light as seen by increased adenosine triphosphate, cytochrome c oxidase and membrane potentials. This thesis aims to assess contributing factors to ageing and AMD, photoreceptor ageing in mice and humans, (healthy-aged adults and patients with AMD), and evaluate the effect of 670nm light on these parameters. The role of CFH in retinal development was evaluated. From birth, Cfh-/- mice have significantly disrupted and delayed retinal development revealing that in this AMD model there is a developmental footprint. Then, photoreceptor function (ERG) was measured in 7 month and 12 month C57/BL6 mice. The age-related reductions in retinal function improved with 670nm exposure. Similar effects were seen in aged Cfh-/-. Markers of cytochrome c-oxidase, reactive oxygen species and retinal stress (vimentin) also showed improvements in those time frames. Furthermore, short term exposure to 670nm (20 minutes) lead to an improvement in photoreceptor function, measured by ERG. This returned to normal in one week. However, ATP levels did not increase in vivo. Finally, 8 months exposure to 670nm light in aged mice significantly reduced age-related photoreceptor loss. In humans, cone function was shown to decline with age. This was measured with a hand-held ERG device. This correlated with chronological and biological ageing. Finally, 670nm light treatment over one month in 30 patients with AMD improved scotopic thresholds and visual acuity. These results were not replicated in healthy-aged adults. This thesis has translated animal studies into a clinical trial in humans that has shown promise