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Gerard Lutty, Imran Bhutto, Johanna Seddon, D. McLeod; Mast Cell Degranulation in AMD Choroid. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3051.
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Mast cells (MCs) are effector cells of the innate immune system and are inhabitants of most mammalian choroids. They are activated by complement (C5a), IgE, and many microorganisms. When activated, they degranulate, releasing a plethora of proteases, growth factors, endoglycosidases, histamine, and lipid metabolites. The purpose of this study was to determine MC numbers and their degranulation in age-related macular degeneration (AMD) compared to aged choroidal tissues.
Human postmortem eyes were obtained within 24 hours post mortem. Retina was excised from the eye cup and then the choroid dissected intact. RPE was left on the choroid so the area of RPE atrophy could be mapped in geographic atrophy eyes (GA). The choroid was incubated for alkaline phosphatase enzyme activity yielding a blue formazan reaction product in viable blood vessels. After washing, the tissue was also incubated for nonspecific esterase activity, which labels MCs and granulocytes as published previously (Lutty et al, A J Path 1997). The choroid was then partially bleached and counts of mast cells were made in at least three fields in each area of choroid.
Human choroid had MCs randomly dispersed. The number of nondegranulated MCs in submacular choroid was greater in all groups than temporal equatorial choroid. Although the number of nondegranulated MCs was similar in submacular choroid between the GA subjects and controls (mean mean 97.7 +/- 45.8/mm2 vs 90.3 +/- 94.9/mm2), the number of degranulated MCs was significantly greater in the GA submacular choroid (76.9 +/- 45.2 vs 2.8 +/- 10/mm2, p<0.0001 using unpaired t test with Welch corrections). Also, the GA subject had significantly less degranulated MCs in temporal equatorial choroid than submacular (76.9 +/- 45.2 vs 6.9 +/- 9.2/mm2, p<0.0001). One control eye was note worthy: this had the highest mast cell counts of all eyes (215.7/mm2 in macula and 83/mm2 at equator) and the subject had fibromyalgia, which increases mast cell numbers in skin. However, none of the mast cells were degranulated in this subject.
The significantly higher number of degranulated mast cells in GA submacular choroid suggests that mast cell degranulation may contribute to the pathologic decline of this tissue in GA. The proteases released in degranulation could degrade the choroidal stroma and Bruchs membrane and cause death of RPE and endothelial cells, while the cytokines released can attract macrophages.
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