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

As the bright light dims: loss of lipofuscin-attributable autofluorescence from RPE in aging and AMD

Meeting Abstract

  • Thomas Ach - Würzburg
  • R.T. Smith - New York
  • Z. Ablonczy - Charleston
  • J. Hillenkamp - Würzburg
  • R. Heintzmann - Jena
  • K.R. Sloan - Birmingham
  • C.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. Doc15amd30

doi: 10.3205/15amd30, urn:nbn:de:0183-15amd304

Veröffentlicht: 1. Oktober 2015

© 2015 Ach et al.
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

Background: In healthy persons, fundus autofluorescence (AF) intensity diminishes after age 70 [1], with the underlying mechanisms still unknown. In age-related macular degeneration (AMD), hypoautofluorescent areas in fundus AF-imaging are often referred to as retinal pigment epithelium (RPE) atrophy; however, how atrophy starts in individual cells is not known. This microscopy study uses human RPE-flatmounts to demonstrate possible mechanisms, which lead to the formation of hypoautofluorescent areas in the RPE cell layer.

Methods: From 35 human donor eyes (25 AMD (>69 years); 10 age-matched controls), RPE-flatmounts were prepared. RPE cells were systematically imaged at >1300 predefined locations twofold:

1) using a spinning-disk confocal fluorescence microscope, RPE lipofuscin/melanolipofuscin AF (exc. 488, em. >510nm) and RPE cytoskeleton (labeled with AlexaPhalloidin647);

2) using high-resolution structured illumination microscopy (SIM), RPE-AF granules were imaged at locations chosen by an unbiased sampling scheme.

Results: In normal aging, hypofluorescence is attributable to:

1) RPE cells densely packed with melanosomes, or

2) degranulation (loss of individual AF granules).

In AMD, hypofluorescence results from:

1) degranulation (as in normal aging), or

2) aggregation and shedding into the sub-RPE space. All these mechanisms lead to a diminished AF signal in the en face view.

Aggregates (5-20 µm in diameter) in AMD RPE-flatmounts comprise multiple AF granules, and multiple aggregates can be found in a single RPE cell.

Conclusion: For the first time, possible mechanisms leading to reduced RPE-AF in normal aging and AMD, are demonstrated on a histological basis. An overall reduced AF intensity in older adults might be explained by a slow but steady loss of individual granules (shed into the sub-retinal and sub-RPE space), while in AMD the shedding of aggregates of individual cells (shed basolaterally into basal laminar deposits) leads to circumscribed areas of reduced RPE-AF. These results can help to further interpret clinical fundus AF findings.


References

1.
Delori FC, Goger DG, Dorey CK. Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1855-66.