The therapeutic potential of 670nm light in retinal degeneration

Abstract

The retina is susceptible to degenerative changes over the natural life-span, owing to a range of different factors, including genetic susceptibility and environmental and lifestyle factors such as smoking, diet and exposure to bright light. Photoreceptors, with their high metabolic demands and polyunsaturated fatty acid (PUFA)-rich outer segments (OS), are the most vulnerable of retinal cells, being sensitive to oxidative damage and inflammatory attack, resulting in cell death. Because the health and stability of the photoreceptors is essential to the maintenance of functional vision, rescue strategies aimed at stabilising photoreceptors are of critical importance. Exposure to electromagnetic wavelengths in the far-red (FR) to near-infrared (NIR) range (600nm-1000nm) has been reported to have beneficial effects for mammalian tissues in a variety of contexts. These include treatment of soft tissue injuries, radiation-induced ulcers, inflammatory conditions and neurodegenerative diseases. In the recent years, there has been an increasing interest in the use of 670nm red light to manage retinal injuries. The work presented in this thesis examines the effects of exposure to 670nm light in two established models of retinal degeneration in vivo; a light damage (LD) model using Sprague Dawley rats, and an oxygen-induced model of retinal degeneration (hyperoxia) using the C57Bl/6J mouse. The findings indicate that irradiation with 670nm light ameliorates retinal damage in both models, and its effects include modulation of gene expression. In the LD model, irradiation with 670nm light mitigates the damaging effects of white light in a dose-dependent manner, reducing measures of oxidative damage and inflammatory response. In the hyperoxia model, irradiation with 670nm light reduces photoreceptor cell death, mitigates oxidative stress, preserves the integrity of outer retinal barrier and slows down, but does not inhibit, retinal degeneration. The results provide evidence supporting the therapeutic potential of 670nm light in the treatment of retinal degenerative conditions where oxidative stress, cell death and inflammation are involved, particularly in the early stages of degeneration.