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Hyperglycaemia appears to be a critical factor in the aetiology of diabetic retinopathy and initiates downstream events including: basement membrane thickening, pericyte drop out and retinal capillary non-perfusion. More recently, focus has been directed to the molecular basis of the disease process in diabetic retinopathy. Of particular importance in the development and progression of diabetic retinopathy is the role of growth factors (eg vascular endothelial growth factor, placenta growth factor and pigment epithelium-derived factor) together with specific receptors and obligate components of the signal transduction pathway needed to support them. Despite these advances there are still a number of important questions that remain to be answered before we can confidently target pathological signals. How does hyperglycaemia regulate retinal vessels? Which growth factors are most important and at what stage of retinopathy do they operate? What is the preferred point in the growth factor signalling cascade for therapeutic intervention? Answers to these questions will provide the basis for new therapeutic interventions in a debilitating ocular condition.

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Exposure of the eye to intense light, particularly blue light, can cause irreversible, oxygen-dependent damage to the retina. However, no key chromophores that trigger such photooxidative processes have been identified yet. We have found that illumination of human retinal pigment epithelium (RPE) cells with light induces significant uptake of oxygen that is both wavelength- and age-dependent. Analysis of photoreactivity of RPE cells and their age pigment lipofuscin indicates that the observed photoreactivity in RPE cells is primarily due to the presence of lipofuscin, which, under aerobic conditions, generates several oxygen-reactive species including singlet oxygen, superoxide anion, and hydrogen peroxide. We have also found that lipofuscin-photosensitized aerobic reactions lead to enhanced lipid peroxidation as measured by accumulation of lipid hydroperoxides and malondialdehyde in illuminated pigment granules. Hydrogen peroxide is only a minor product of aerobic photoexcitation of lipofuscin. We postulate that lipofuscin is a potential photosensitizer that may increase the risk of retinal photodamage and contribute to the development of age-related maculopathy.