The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Lipofuscin Redistribution and Loss Accompanied by Cytoskeletal Stress in Retinal Pigment Epithelium of Eyes With Age-Related Macular Degeneration
Open accessAbstract
PURPOSE: Lipofuscin (LF) and melanolipofuscin (MLF) of the retinal pigment epithelium (RPE) are the principal sources of autofluorescence (AF) signals in clinical fundus-AF imaging. Few details about the subcellular distribution of AF organelles in AMD are available. We describe the impact of aging and AMD on RPE morphology revealed by the distribution of AF LF/MLF granules and actin cytoskeleton in human tissues. METHODS: Thirty-five RPE-Bruch's membrane flatmounts from 35 donors were prepared (postmortem: ≤4 hours). Ex vivo fundus examination at the time of accession revealed either absence of chorioretinal pathologies (10 tissues; mean age: 83.0 ± 2.6 years) or stages of AMD (25 tissues; 85.0 ± 5.8 years): early AMD, geographic atrophy, and late exudative AMD. Retinal pigment epithelium cytoskeleton was labeled with AlexaFluor647-Phalloidin. Tissues were imaged on a spinning-disk fluorescence microscope and a high-resolution structured illumination microscope. RESULTS: Age-related macular degeneration impacts individual RPE cells by (1) lipofuscin redistribution by (i) degranulation (granule-by-granule loss) and/or (ii) aggregation and apparent shedding into the extracellular space; (2) enlarged RPE cell area and conversion from convex to irregular and sometimes concave polygons; and (3) cytoskeleton derangement including separations and breaks around subretinal deposits, thickening, and stress fibers. CONCLUSIONS: We report an extensive and systematic en face analysis of LF/MLF-AF in AMD eyes. Redistribution and loss of AF granules are among the earliest AMD changes and could reduce fundus AF signal attributable to RPE at these locations. Data can enhance the interpretation of clinical fundus-AF and provide a basis for future quantitative studies.
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Cites
Physiology of cell volume regulation in vertebrates
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Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
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Actin stress fibers – assembly, dynamics and biological roles
Tojkander, S., Gateva, G., & Lappalainen, P. (2012) · Journal of Cell Science · doi:10.1242/jcs.098087 · Cited by 900
Ageing and degeneration in the macular region: A clinico-pathological study
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Oxidative damage-induced inflammation initiates age-related macular degeneration
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An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice
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DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
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Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration
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Cited by
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 802
Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration
Kaarniranta, K., Uusitalo, H., Blasiak, J., Felszeghy, S., Kannan, R., Kauppinen, A., Salminen, A., Sinha, D., & Ferrington, D. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100858 · Cited by 526
cGAS drives noncanonical-inflammasome activation in age-related macular degeneration
Kerur, N., Fukuda, S., Banerjee, D., Kim, Y., Fu, D., Apicella, I., Varshney, A., Yasuma, R., Fowler, B. J., Baghdasaryan, E., et al. (2018) · Nature Medicine · doi:10.1038/nm.4450 · Cited by 286
Balaratnasingam, C., Messinger, J. D., Sloan, K. R., Yannuzzi, L. A., Freund, K. B., & Curcio, C. A. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2016.12.034 · Cited by 174
Self-citationZanzottera, E. C., Messinger, J. D., Ach, T., Smith, R. T., Freund, K. B., & Curcio, C. A. (2015) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.15-16431 · Cited by 164
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Metadata
- Authors
- Ach, T., Tolstik, E., Messinger, J. D., Zarubina, A. V., Heintzmann, R., & Curcio, C. A.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2015-05-21
- Volume
- 56
- Issue
- 5
- Pages
- 3242
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2334245029
- Cited by
- 174
- References
- 14
- FWCI
- 15.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
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