September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Bruch’s Membrane is Leaky and RPE lacks Apoptosis, Autophagy and Lysosomes in AMD
Author Affiliations & Notes
  • Mones S Abu-Asab
    Histology Section, National Eye Institute, Bethesda, Maryland, United States
  • Christopher P Ardeljan
    Histology Section, National Eye Institute, Bethesda, Maryland, United States
  • Maria Mercedes Campos
    Histology Section, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Mones Abu-Asab, None; Christopher Ardeljan, None; Maria Campos, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6033. doi:
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    • Get Citation

      Mones S Abu-Asab, Christopher P Ardeljan, Maria Mercedes Campos; Bruch’s Membrane is Leaky and RPE lacks Apoptosis, Autophagy and Lysosomes in AMD. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6033.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : This study aims to interpret the ultrastructural aberrations in RPE and Bruch’s membrane of AMD in order to identify contributing factors to its etiology. Very few published ultrastructural reports on AMD have identified pathological abnormalities in RPE and Bruch’s membrane. We have observed that some aberrations could cause the accumulation of drusen and cellular debris, as well as other abnormalities. We are also investigating whether changes within the macula differ from those in the peripheral fundus.

Methods : Ultrastructural examination of Bruch’s membrane and RPE, from the macula and peripheral fundus, was performed on the eyes of 7 AMD donors, all of whom were over 80 years old. Eyes were fixed in formalin and samples from the macula and temporal fundus were dissected out. Preparation for TEM was done as follows: tissues were embedded in epoxy resin, sectioned, double-stained with uranyl acetate and lead citrate, and viewed with a JOEL JM-1010 TEM.

Results : Ultrastructural aberrations were seen in all of the examined specimens. Normal and necrotic RPE cells appeared without lysosomes or autophagosomes, and none of the specimens had apoptotic RPE cells. In some specimens, the RPE layer had doubled by producing a new healthy layer of cells on top of the older degenerate one. Drusen and debris of necrotic cells were present below the RPE layer. Bruch’s membrane was leaky, allowing drusen contents and cellular debris of necrotic RPE cells to pass from the RPE side onto the choroidal side; these encompassed lipid droplets, lipofuscin, chromatin vesicles, degenerate melanosomes, and aqueous vesicles. Additionally, Bruch’s membrane showed collagen degeneration and loss of elastin.

Conclusions : Our survey of AMD specimens revealed a number of ultrastructural aberrations, some of which have not been previously described in AMD. These RPE aberrations indicate dysfunctional cellular clearance mechanisms such as apoptosis, lysosomes, and autophagy. Lack of apoptosis seems to be forcing RPE cells into necrosis leading to an accumulation of cellular debris on top of and within Bruch’s membrane. Debris is also being passed onto the choroidal side of Bruch’s membrane. Necrosis and not apoptosis appears to be the prominent type of cell death in AMD. Both the macular and peripheral regions shared the same abnormalities and there was no significant differences between them.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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