Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and retina.
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.
Mullins
Robert F
RF
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
Skeie
Jessica M
JM
Malone
Elizabeth A
EA
Kuehn
Markus H
MH
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
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1