Increased choroidal mast cells and their degranulation in age-related macular degeneration

Imran A. Bhutto, D. Scott McLeod, Tian Jing, Janet S. Sunness, Johanna M. Seddon, Gerard Anthony Lutty

Research output: Contribution to journalArticle

Abstract

Background/aims 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 nonspecific 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/ mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; 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). Conclusion 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.

Original languageEnglish (US)
JournalBritish Journal of Ophthalmology
DOIs
StateAccepted/In press - Mar 1 2016

Fingerprint

Cell Degranulation
Macular Degeneration
Mast Cells
Choroid
Choroidal Neovascularization
Geographic Atrophy
Carboxylesterase
Retinal Pigments
Alkaline Phosphatase
Blood Vessels
Peptide Hydrolases
Cell Count

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Increased choroidal mast cells and their degranulation in age-related macular degeneration. / Bhutto, Imran A.; McLeod, D. Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard Anthony.

In: British Journal of Ophthalmology, 01.03.2016.

Research output: Contribution to journalArticle

@article{f820f27d37b64c9c9957877a3d3d6591,
title = "Increased choroidal mast cells and their degranulation in age-related macular degeneration",
abstract = "Background/aims 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 nonspecific 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/ mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; 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). Conclusion 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.",
author = "Bhutto, {Imran A.} and McLeod, {D. Scott} and Tian Jing and Sunness, {Janet S.} and Seddon, {Johanna M.} and Lutty, {Gerard Anthony}",
year = "2016",
month = "3",
day = "1",
doi = "10.1136/bjophthalmol-2015-308290",
language = "English (US)",
journal = "British Journal of Ophthalmology",
issn = "0007-1161",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Increased choroidal mast cells and their degranulation in age-related macular degeneration

AU - Bhutto, Imran A.

AU - McLeod, D. Scott

AU - Jing, Tian

AU - Sunness, Janet S.

AU - Seddon, Johanna M.

AU - Lutty, Gerard Anthony

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background/aims 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 nonspecific 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/ mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; 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). Conclusion 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.

AB - Background/aims 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 nonspecific 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/ mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; 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). Conclusion 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.

UR - http://www.scopus.com/inward/record.url?scp=84960847385&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960847385&partnerID=8YFLogxK

U2 - 10.1136/bjophthalmol-2015-308290

DO - 10.1136/bjophthalmol-2015-308290

M3 - Article

C2 - 26931413

AN - SCOPUS:84960847385

JO - British Journal of Ophthalmology

JF - British Journal of Ophthalmology

SN - 0007-1161

ER -