Age‐dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice
Abstract
Summary: Fundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages. Increasingly strong AF signals were observed with age in the neuroretina and subretinal/RPE layer by confocal scanning laser ophthalmoscopy. Unlike fundus AF detected in normal human subjects, mouse fundus AF appeared as discrete foci distributed throughout the retina. Most of the AF signals in the neuroretina were distributed around retinal vessels. Confocal microscopy of retinal and choroid/RPE flat mounts demonstrated that most of the AF signals were derived from Iba‐1+ perivascular and subretinal microglia. An age‐dependent accumulation of Iba‐1+ microglia at the subretinal space was observed. Lipofuscin granules were detected in large numbers in subretinal microglia by electron microscopy. The number of AF+ microglia and the amount of AF granules/cell increased with age. AF granules/lipofuscin were also observed in RPE cells in mice older than 12 months, but the number of AF+ RPE cells was very low (1.48 mm−2 and 5.02 mm−2 for 12 and 24 months, respectively) compared to the number of AF+ microglial cells (20.63 mm−2 and 76.36 mm−2 for 6 and 24 months, respectively). The fluorescence emission fingerprints of AF granules in subretinal microglia were the same as those in RPE cells. Our observation suggests that perivascular and subretinal microglia are the main cells producing lipofuscin in normal aged mouse retina and are responsible for in vivo fundus AF. Microglia may play an important role in retinal aging and age‐related retinal diseases.
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Microglial phagocytosis and migration are hallmark processes affected in the aging retina.
“hallmark processes affected in the aging retina (59–61).”
From Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice (2025) · cites this paper as [61]
Aged microglia tend to accumulate lipofuscin, which has been associated with dysfunction and inflammation.
“Aged microglia also tend to accumulate lipofuscin [52–54], aggregations of highly oxidized proteins cross-linked with sugars and lipids [55], which have been associated with dysfunction and inflammation [56,57].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [54]
Lipofuscin has been shown to accumulate in aged microglia and is generally considered a hallmark of aging.
“Lipofuscin has been shown to accumulate in aged microglia [52–54], and is generally considered a hallmark of aging [150].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [54]
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- Authors
- Xu, H., Chen, M., Manivannan, A., Lois, N., & Forrester, J. V.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Xu, Heping
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2007-11-06
- Volume
- 7
- Issue
- 1
- Pages
- 58-68
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1996703105
- Cited by
- 277
- References
- 53
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 14 · 2021: 25 · 2020: 12 · 2019: 12 · 2018: 18 · 2017: 13 · 2016: 18 · 2015: 18 · 2014: 16 · 2013: 20 · 2012: 15
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Research Councils UK
- Office of Science
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- lipofuscin, fundus autofluorescence, microglia, retinal pigment epithelium, retinal aging, perivascular microglia, Iba1, confocal scanning laser ophthalmoscopy, confocal microscopy, C57BL/6 mice
- MeSH terms
- Aging, Animals, Calcium-Binding Proteins, Choroid, Lipofuscin, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Retina, Retinal Vessels, Microglia, Microscopy, Confocal, Microscopy, Electron, Transmission, Mice
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