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Updated: May 25, 2026
Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures
Published on: April 14, 2023
Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys
Sylvie Julien1, Ulrich Schraermeyer
1Section of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tübingen, Germany.
Abstract:
Lipofuscin is a cytologic hallmark of aging in metabolically active postmitotic cells including neurons, cardiac muscle cells, and the retinal pigment epithelium (RPE). High levels of lipofuscin are involved in the pathogenesis of age-related macular degeneration (AMD), the main cause of blindness in the elderly population in the western world. Degradation and exocytosis of lipofuscin by RPE cells have not been observed in vivo until now, and no drug is known to eliminate the intracellular amount of lipofuscin. Here, we show that in monkeys treated with a small molecule belonging to the tetrahydropyridoethers class (n = 36 of 48 monkeys), RPE cells significantly release lipofuscin. In 4 eyes, macrophages were detected which had taken up lipofuscin. They were located between the Bruch's membrane and the RPE, and in the choroid. The quantification of pigment granules was performed by transmission electron microscopy. Our findings open the way to develop therapeutic strategies to remove lipofuscin from RPE cells, which may have implications for the treatment of age-related macular degeneration in which lipofuscin accumulation in cells is a causative factor.
Insights
A new drug treatment helps retinal pigment epithelium cells release lipofuscin, a key factor in age-related macular degeneration. This discovery offers potential new therapies for treating vision loss associated with aging.
Area of Science:
- Ophthalmology
- Cell Biology
- Gerontology
Background:
- Lipofuscin accumulation is a hallmark of cellular aging, particularly in neurons, cardiac cells, and retinal pigment epithelium (RPE).
- High lipofuscin levels in RPE cells are implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness.
- Previously, in vivo degradation or exocytosis of lipofuscin by RPE cells and effective drugs to reduce intracellular lipofuscin were unknown.
Purpose of the Study:
- To investigate the effect of a novel tetrahydropyridoethers class molecule on lipofuscin levels in RPE cells.
- To determine if RPE cells can release lipofuscin in vivo.
- To explore potential therapeutic strategies for AMD by targeting lipofuscin accumulation.
Main Methods:
- Treatment of 48 monkeys with a small molecule from the tetrahydropyridoethers class.
- In vivo observation of RPE cells for lipofuscin release.
- Detection and localization of macrophages engulfing lipofuscin using transmission electron microscopy.
- Quantification of pigment granules via transmission electron microscopy.
Main Results:
- Monkeys treated with the tetrahydropyridoethers molecule showed significant lipofuscin release from RPE cells.
- Macrophages were observed internalizing released lipofuscin, located between Bruch's membrane and RPE, and within the choroid.
- This study provides the first in vivo evidence of RPE cells releasing lipofuscin.
Conclusions:
- The tested small molecule promotes the release of lipofuscin from RPE cells.
- This mechanism involves macrophages potentially clearing the released lipofuscin.
- These findings present a promising therapeutic avenue for treating AMD by reducing lipofuscin burden in RPE cells.
