title: Increased choroidal mast cells and their degranulation in age-related macular degeneration.
abstract: OBJECTIVE
  Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD.
  
  
  METHODS
  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 non-specific esterase activities (MCs). Degranulated (DG) and non-degranulated MCs in four areas of posterior choroid (nasal, non-macular, paramacular and submacular) were counted in flat mounts (4-6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses.
  
  
  RESULTS
  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/mm(2); p=0.0091) and GA (199.08±82.0 cells/mm(2); p=0.0019) compared with the aged controls. DG MCs were 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 MCs had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity with CC in GA and exudative AMD and in choroidal neovascularisation (CNV).
  
  
  CONCLUSIONS
  Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and retinal pigment epithelial and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid.
authors.affiliation: Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors.forename: Imran A
authors.initials: IA
authors.lastname: Bhutto
authors.affiliation: Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McLeod
authors.affiliation: Biostatistics Consulting Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Jing
authors.affiliation: Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, Baltimore, Maryland, USA Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sunness
authors.affiliation: Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Boston, Massachusetts, USA Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Seddon
authors.affiliation: Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Lutty
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D015550:Cell Degranulation; D015862:Choroid Diseases / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D057092:Geographic Atrophy / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D034721:Mastocytosis, Systemic / Q000175:diagnosis* / Q000378:metabolism; D008875:Middle Aged; D014019:Tissue Donors; D057135:Wet Macular Degeneration / Q000175:diagnosis*
keywords: Choroid; Inflammation; Macula; Neovascularisation; Pathology