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Imran Ahmed Bhutto, D. Scott McLeod, Jing Tian, Rachel E Silver, Johanna M Seddon, Gerard A Lutty; Increased choroidal mast cells and their degranulation in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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Inflammation has been implicated in age-related macular degeneration (AMD). Mast cells (MCs) play a key role in the inflammatory process. When activated, these connective tissue residents release granules rich in histamine, proteases and cytokines into the interstitium. The association of choroidal MC with pathological changes in AMD has not been previously investigated. This study examines the association of MCs, a resident choroidal inflammatory cell, with pathological changes in AMD.
Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated for alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid were counted (4~6 fields/area) in flat mounts. Choroids were subsequently embedded in JB-4 and semi thin sectioned for histological quantitative analyses. Two-tailed Student’s t-test and Wilcoxon test were used for statistical analysis.
The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA choroids (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacular choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed at Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV).
Increased MC degranulation was observed in all AMD choroids. Degranulation was often associated with pathological changes in the CC. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid.
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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