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The human retinal pigment epithelial (RPE) layer contains a complex mixture of components called lipofuscin; this mixture forms with age and with various genetic disorders such as Stargardt's disease. Its presence may contribute to retinal deterioration via several mechanisms including photochemical processes. In the lipofuscin mixture, both type I and II mechanisms have been identified, with the latter consisting of the generation of singlet oxygen. Several components of that mixture have been identified, most notably a bis-retinoid pyridinium compound called A2E and its derivatives. Photooxidative studies on the compound A2E have revealed that its dominant photochemical mechanism is via free radical or type I processes. Because singlet oxygen is an important photooxidative intermediate in tissue, its generation in the RPE may contribute to retinal maculopathies. It is therefore necessary to determine which specific component(s) in the lipofuscin mixture produce singlet oxygen upon excitation with light. This was ascertained by evaluating the action spectrum for singlet oxygen production for the whole lipofuscin mixture using time-resolved spectroscopy. Singlet oxygen was generated by excitation of the sample at different wavelengths while maintaining a constant beam energy, and was directly detected by its phosphorescence decay at 1270 nm using a Ge photodiode. The action spectrum for singlet oxygen sensitization by the organic soluble portion of lipofuscin had an absorption maximum at ca 380 nm, which is to the blue of A2E (maximum at 430 nm). Compounds with a similar absorption maximum eluted in the HPLC earlier than A2E and were detected in human lipofuscin. The concentration of this component apparently increased in concentration in human RPE lipofuscin mixture as a function of age up to 90 years old.

The progressive loss of visual faculties with advancing age is attributed, sometimes, mainly to allegedly inevitable optical deterioration, such as clouding of the media, or again to neurosenescence, as typified by cell-death. The relevant factors are assessed, and it is not thought likely that changes in normal ocular optics account for changes in contrast sensitivity and visual acuity with age. The role of senescent changes in the retina is analyzed. The progressive temporal and spatial patterns of the accumulation of lipofuscin in the retinal pigment epithelium (RPE) and the putative control of its concentration by the crystalline lens are examined following an earlier suggestion that lenticular UVA transmissivity may control the rate of UVA entry into the eye and so perhaps the amount of lipofuscin formed in the RPE. It is suggested that morphological changes attributed to senescence may partly be due to cumyulative effects of irradiation.