title: Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and retina.
abstract: OBJECTIVE
  In order to understand the extent of choriocapillary endothelial cell activation in different topographic regions of the eye, we sought to compare the localization of intercellular adhesion molecule-1 (ICAM-1) in macular and peripheral regions of human eyes.
  
  
  METHODS
  Sections of sucrose-embedded human donor eyes that included the macula and ora serrata were evaluated for ICAM-1 and ICAM-2 immunoreactivity with monoclonal and polyclonal antibodies. Patterns of ICAM-1 labeling in peripheral and macular regions were examined in 20 eyes. Morphometric analyses of anti-ICAM-1 labeling intensity in the choriocapillaris were performed using ImageJ software on a series of macular and extramacular punches from nine eyes. Quantitative PCR analysis for ICAM-1 mRNA was performed on the RPE-choroid from the same regions from six of the same eyes, and Western blots of samples treated or untreated with N-glycosidase were performed to compare retinal and choroidal ICAM-1.
  
  
  RESULTS
  ICAM-1 labeling of the choriocapillaris was typically more intense in the macula than in the peripheral choroid in human donor eyes (14/20). ICAM-2 was also detected in the choriocapillaris and retinal vessels. Morphometric measurements confirmed a significant macular-extramacular difference in ICAM-1 in six of nine eyes (p<0.05), with 1 of 9 eyes showing the opposite pattern. This pattern was not noted for endogenous alkaline phosphatase or ICAM-2. The opposite pattern was noted in the external limiting membrane (ELM), which exhibited more intense ICAM-1 labeling in the far periphery than in the macula. On Western blots, choroidal ICAM-1 exhibited a greater molecular weight than the retinal form, with most of the apparent weight difference due to N-linked carbohydrate chains.
  
  
  CONCLUSIONS
  The regional differences in ICAM-1 distribution in the choriocapillaris may indicate that this region is subject to increased leukocyte trafficking. In view of the role of inflammatory processes in age-related macular degeneration (AMD), we propose that the higher level of ICAM-1 protein in the macular choriocapillaris may impart greater susceptibility of the macula to immune cell-mediated damage in AMD.
authors.affiliation: Center for Macular Degeneration, Department of Ophthalmology and Visual Science, The University of Iowa Carver College of Medicine, Iowa City, IA, USA. robert-mullins@uiowa.edu
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Skeie
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Malone
authors.forename: Markus H
authors.initials: MH
authors.lastname: Kuehn
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002829:Choroid / Q000098:blood supply*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008266:Macula Lutea / Q000098:blood supply*; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1