Influence of dietary vitamin A on autofluorescence of leupeptin-induced inclusions in the retinal pigment epithelium.

Substantial evidence indicates that the major precursors for retinal pigment epithelial (RPE) lipofuscin are molecular components of the photoreceptor outer segments. Previous experiments have demonstrated that the retinoids required for transduction by the photoreceptors promote RPE lipofuscin fluorophore formation. Animals deficient in these retinoids accumulate lipofuscin in the RPE at greatly reduced rates. The protein components of the photoreceptor outer segments also appear to be involved in the formation of RPE lipofuscin fluorophores. When degradation of phagocytosed photoreceptor outer segment proteins by the RPE is blocked, this tissue rapidly becomes engorged with phagosome-derived inclusions that have fluorescence properties similar to lipofuscin. Experiments were conducted to determine whether the development of lipofuscin-like fluorescence in these inclusions was dependent on the availability of retinoids. Rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After the retinas of the -A animals had been depleted of retinoids involved in vision, animals from both groups were given intraocular injections of the protease inhibitor leupeptin. Two days later, the amounts of lipofuscin-like autofluorescence from the RPEs of rats in each group were determined. Leupeptin treatment produced an increase in this fluorescence in RPEs of the +A animals, but not in the RPEs of the rats fed the -A diet, despite the fact that phagosome-like inclusions accumulated in the RPE in both dietary groups. This finding suggests that retinoids involved in the visual process are probably directly involved in RPE lipofuscin fluorophore formation.