Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration

Investigative Ophthalmology & Visual Science
T AchChristine A Curcio

Abstract

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. 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. 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 an...Continue Reading

Citations

Mar 25, 2016·Acta Ophthalmologica·Peep V AlgvereStefan Seregard
Aug 1, 2015·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Patrick PallittoJulia Herrmann
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Jun 22, 2018·Disease Models & Mechanisms·Meng ZhangNady Golestaneh
Dec 5, 2018·Investigative Ophthalmology & Visual Science·Charles E GrangerEthan A Rossi
Nov 28, 2017·Nature Medicine·Nagaraj KerurJayakrishna Ambati
May 22, 2018·Retina·Maximilian PfauUNKNOWN Fundus Autofluorescence in Age-Related Macular Degeneration Study Group
Aug 14, 2019·Investigative Ophthalmology & Visual Science·Qitao ZhangJason M L Miller
Mar 7, 2020·Journal of Pineal Research·Hernán H DiéguezDamián Dorfman
Jul 11, 2020·Investigative Ophthalmology & Visual Science·Andreas PollreiszChristine A Curcio
Jul 14, 2020·Investigative Ophthalmology & Visual Science·Vera L BonilhaJoe G Hollyfield
Jul 15, 2020·Investigative Ophthalmology & Visual Science·Tu M TranGlenn Yiu
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Audrey VoisinNicolas Leveziel
Oct 20, 2018·Ophthalmic Surgery, Lasers & Imaging Retina·Jorge Orellana-RiosR Theodore Smith
Sep 9, 2020·Investigative Ophthalmology & Visual Science·Rowena SchultzMartin Hammer
Sep 29, 2020·Journal of Inflammation Research·Mohd Imran Khan, Gururao Hariprasad
Aug 29, 2020·Translational Vision Science & Technology·Nikolai KleefeldtThomas Ach
Apr 30, 2017·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·R SemécasC Chiquet
Jan 30, 2019·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Martin Dominik LeclairePeter Heiduschka
Jun 8, 2019·Investigative Ophthalmology & Visual Science·J Alan GambrilChristine A Curcio
Jul 25, 2019·International Journal of Molecular Sciences·Ioana-Sandra TarauThomas Ach
May 6, 2019·Investigative Ophthalmology & Visual Science·Gregor Sebastian ReiterAndreas Pollreisz

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