Impact of lipofuscin on the retinal pigment epithelium: electroretinographic evaluation of a protease inhibition model

With aging, the retinal pigment epithelium (RPE) becomes increasingly congested with residual debris called lipofuscin. Little is known about the impact of lipofuscin on retinal function, and this was addressed in the present study by examining the influence of RPE debris on electroretinographic (ERG) parameters utilizing an experimental model of lipofuscin accumulation. Pigmented rats were injected intravitreally with the protease inhibitor leupeptin, and examined 1 week later by electroretinogram (ERG) recording and light and electron microscopy. Relative to vehicle-injected controls, leupeptin-treated retinas showed abundant accumulation throughout the RPE cytoplasm of inclusions that resembled lipofuscin. RPE cells filled with this debris showed a marked increase in height and a displacement of melanin from their apical border. Morphological changes in the RPE had no influence on retinal function since ERG threshold, a- and b-wave maximum amplitude, latency and implicit time were not significantly different between leupeptin-treated eyes and controls. Furthermore, leupeptin-induced RPE inclusions did not alter either the rate or extent of ERG dark adaptation. These findings suggest that filling of the RPE cytoplasm with residual debris is not in itself likely to be the cause of functional alterations in the aging eye.