gms | German Medical Science

VI. International Symposium on AMD – Age-Related Macular Degeneration – Emerging Concepts – Exploring known and Identifying new Pathways

11. - 12.09.2015, Baden-Baden

Visualizing RPE fate in AMD with histology and optical coherence tomography

Meeting Abstract

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  • Christine A. Curcio - Birmingham

VI. International Symposium on AMD – Age-Related Macular Degeneration – Emerging Concepts – Exploring known and Identifying new Pathways. Baden-Baden, 11.-12.09.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15amd11

doi: 10.3205/15amd11, urn:nbn:de:0183-15amd114

Veröffentlicht: 1. Oktober 2015

© 2015 Curcio.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

The compartmentalization of light scattering organelles in photoreceptors and retinal pigment epithelium (RPE) makes it possible to assign the four outer retinal hyperreflective bands of spectral domain optical coherence tomography (SDOCT) to specific subcellular sources. Histological analysis of short post-mortem human donor eyes with age-related macular degeneration (AMD) supports mitochondria, melanosomes, and lysosomes as independent reflectivity sources. Using high-resolution histology of 52 late AMD eyes, RPE specific markers (melanosomes, lipofuscin, and basal laminar deposit), and unbiased sampling techniques, we determined the frequency of occurrence of 11 phenotypes of RPE and 3 phenotypes of RPE-derived cells. Our findings are:

1.
Many RPE are in atrophic areas of geographic atrophy (GA) and neovascular AMD eyes.
2.
From outer retinal tubulation of surviving cones and Müller glia, it appears that the biological border of GA is better defined by the external limiting membrane than by the RPE, which may or may not respect this border.
3.
~1/3 of abnormal RPE in GA eyes appear apoptotic and thus actually dying.
4.
The remaining abnormal RPE apparently transdifferentiate to migratory phenotypes, with the layer eventually breaking up as cells leave.
5.
RPE lipofuscin re-distributes and disappears in degeneration; some is shed basolaterally into underlying basal laminar deposit.
6.
Direct clinicopathologic correlation of one case suggests that most RPE phenotypes are visible by current technology SDOCT.
7.
Intraretinal hyperreflective spots can include RPE and non-RPE cells.
8.
Mouse models capture some RPE pathology but not much.
9.
It is possible that RPE change prior to spreading atrophy may serve as a suitable biomarker for clinical trials.
10.
High-resolution histology will enable longitudinal follow-up in large patient populations to achieve an accurate, molecularly informed, and comprehensive natural history of RPE degeneration.

References

1.
Zanzottera EC, Messinger JD, Ach T, Smith RT, Freund KB, Curcio CA. The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2015 May;56(5):3253-68. DOI: 10.1167/iovs.15-16431 Externer Link
2.
Zanzottera EC, Messinger JD, Ach T, Smith RT, Curcio CA. Subducted and melanotic cells in advanced age-related macular degeneration are derived from retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2015 May;56(5):3269-78. DOI: 10.1167/iovs.15-16432 Externer Link
3.
Ach T, Tolstik E, Messinger JD, Zarubina AV, Heintzmann R, Curcio CA. Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015 May;56(5):3242-52. DOI: 10.1167/iovs.14-16274 Externer Link