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Mones S Abu-Asab, Heba Mohammed, Jayram Sastry, Adriana Grewe, Maria M Campos; Choriocapillaris pericyte dropout: an early event in the development of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2434. doi: https://doi.org/.
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Pericytes of the choriocapillaris participate in endothelial formation and stability while supporting vasoconstriction. Although studies have elucidated numerous factors contributing to AMD, the sequence of tissue degeneration and the role of pericyte dropout in AMD progression remains unclear. This study aims to interpret the ultrastructural aberrations that occur in the choriocapillaris pericytes of AMD specimens in order to identify contributing factors to its etiology. Pericyte aberrations as described here support the hypothesis that pericyte dropout could be an early event in the initiation and development of AMD.
A postmortem ultrastructural examination of choriocapillaris’ vessels was performed on the eyes of 7 AMD patients, all over 80 years old. Eyes were fixed in formalin, and the macular and temporal regions were dissected out. Preparation of specimens for TEM was as follows: tissues were embedded in epoxy resin, sectioned, double-stained with uranyl acetate and lead citrate, and viewed with JOEL JM-1010 TEM.
Ultrastructural aberrations revealed that the state of choriocapillaris' pericytes was heterogeneous and fell within 6 observed conditions. These were: 1) pericytes absent in the majority of the capillaries, and the vessels’ basement membranes were surrounded by connective tissue and no remnants of pericytes were visible; 2) pericytes in various states of degeneration; 3) pericytes abnormally located anteriorly (on Bruch’s membrane side); 4) minority of vessels with healthy intact pericytes; 5) thickening of the basement membranes where the thickness extended over the pericytes and some pericytes appeared necrotic while others had healthy cytoplasm; and 6) in cases where the choriocapillaris’ vessels had damaged pericytes, the choroidal vessels at the scleral side had intact pericytes with hypertrophic nuclei.
Only a few pericytes appeared normal; thus, confirming that these perivascular cells undergo degeneration in AMD. The condition of choriocapillaris and RPE in the absence of pericytes is consistent with that seen in diabetic retinopathy cases where the degeneration of pericytes lead to thickening of the basement membrane and perforated vacuolization. Observed endothelial aberrations also support the finding that pericytes play a crucial role in microvascular homeostasis and in vascular recovery after injury.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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