Abstract
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.
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References
Collins M, Brown B (1989) Glare recovery and age related maculopathy. Clin Vis Sci 4:145–153
De La Paz M, Anderson RE (1992) Region and age-dependent variation in susceptibility of the human retina to lipid peroxidation. Invest Ophthalmol Vis Sci 33:3497–3499
Dodt E, Echte K (1961) Dark and light adaptation in pigmented and white rat as measured by electroretinogram threshold. J Neurophysiol 4:427–445
Dowling JE (1960) The chemistry of visual adaptation in the rat. Nature 188:114–118
Dowling JE (1963) Neural and photochemical mechanisms of visual adaptation in the rat. J Gen Physiol 46:459–474
Eisner A, Klein ML, Zillis JD, Watkins MD (1992) Visual function and the subsequent development of exudative age-related macular degeneration. Invest Ophthalmol Vis Sci 33:3091–3102
Eldred GE (1993) Biochemical aging in the retina and RPE. In: Osborne N, Chader G (eds) Progress in retinal research, vol 12. Pergamon, Oxford, pp 101–131
Eldred GE, Lasky MR (1993) Retinal age pigments generated by self-assembling lysosomotropic detergents. Nature 361:724–726
Feeney L (1978) Lipofuscin and melanin of the human retinal pigment epithelium. Fluorescence, enzyme cytochemical and ultrastructural studies. Invest Ophthalmol Vis Sci 17:583–600
Feeney-Burns L, Eldred GE (1983) The fate of the phagosome: conversion to “age pigment” and impact in human retinal pigment epithelium. Trans Ophthalmol Soc U K 103:416–421
Feeney-Burns L, Burns R, Gao C-L (1990) Age-related macular changes in humans over 90 years old. Am J Ophthalmol 109:265–278
Katz ML, Shanker MJ (1989) Development of lipofuscin-like fluorescence in the retinal pigment epithelium in response to protease inhibitor treatment. Mech Ageing Dev 49:23–40
Katz ML, Robison WGJr, Dratz EA (1984) Potential role of autoxidation in age changes of the retina and retinal pigment epithelium of the eye. In: Armstrong D (ed) Free radicals in molecular biology, aging and disease. Raven, New York, pp 163–180
Liem AT, Keunen JEE, Norren DV, Kraats JVD (1991) Rod densitometry in the aging human eye. Invest Ophthalmol Vis Sci 32:2676–2682
Pitts DG (1982) Dark adaptation and aging. J Am Optom Assoc 53:37–41
Wing GL, Blanchard GC, Weiter JJ (1978) The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 17:601–607
Young RW (1976) Visual cells and the concept of renewal. Invest Ophthalmol 15:700–725
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Supported in part by the National Institutes of Health grants EY-04554 and EY-02520, and Research to Prevent Blindness, Inc.
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Rapp, L.M., Fisher, P.L. & Sheinberg, C.H. Impact of lipofuscin on the retinal pigment epithelium: electroretinographic evaluation of a protease inhibition model. Graefe's Arch Clin Exp Ophthalmol 232, 232–237 (1994). https://doi.org/10.1007/BF00184011
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DOI: https://doi.org/10.1007/BF00184011