Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration.
OBJECTIVE
To examine the immunolocalisation of stromal cell derived factor 1 (SDF-1) and its receptor CXCR4 in aged control human donor eyes and eyes with age related macular degeneration (AMD).


METHODS
Postmortem eyes from eight aged control donors (mean age 79.8 years) and from 12 donors with AMD (mean age 83.9 years) were cryopreserved and sectioned through the macular region. SDF-1 and CXCR4 were localised using streptavidin alkaline phosphatase immunohistochemistry and then sections were bleached. Three independent masked observers scored the immunohistochemical reaction product.


RESULTS
In aged control retinas, SDF-1 immunoreactivity was most intense in inner photoreceptor matrix (IPM). CXCR4 showed a similar pattern of immunostaining, but was more prominent in inner segments of photoreceptors. In aged control and AMD choroid, SDF-1 and CXCR4 localisations were most prominent in retinal pigment epithelial (RPE) cells and choroidal stroma. However, the intensity for SDF-1 was significantly reduced in RPE (p < 0.0001) and choroidal stroma (p < 0.05) in late AMD eyes. SDF-1 and CXCR4 immunoreactivities were weak or nearly absent in disciform scars with choroidal neovascularisation (CNV). Circulating cells, presumably leucocytes, were most intensely positive for CXCR4.


CONCLUSIONS
These results show that changes in distribution and relative levels of SDF-1/CXCR4 were not evident in early AMD. This suggests that SDF-1/CXCR4 may not contribute to the formation of CNV in AMD, in that CXCR4+ cells were not incorporated into neovascularisation. However, the examples of CNV studied were within disciform scars, so the authors cannot comment on the role of SDF-1/CXCR4 in the early stages of CNV formation.
Bhutto
I A
IA
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, 21287-9115, USA.
McLeod
D S
DS
Merges
C
C
Hasegawa
T
T
Lutty
G A
GA
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis*; D002829:Choroid / Q000737:chemistry*; D020256:Choroidal Neovascularization / Q000378:metabolism; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010786:Photoreceptor Cells / Q000737:chemistry; D010857:Pigment Epithelium of Eye / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000032:analysis*; D012160:Retina / Q000737:chemistry*
D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4