Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration

被引:32
作者
Bhutto, I. A. [1 ]
McLeod, D. S. [1 ]
Merges, C. [1 ]
Hasegawa, T. [1 ]
Lutty, G. A. [1 ]
机构
[1] Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, Baltimore, MD 21287 USA
关键词
D O I
10.1136/bjo.2006.090357
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Aim: 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.
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页码:906 / 910
页数:5
相关论文
共 41 条
[1]  
Arenberg DA, 1997, METHOD ENZYMOL, V288, P190
[2]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[3]   Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells [J].
Bailey, AS ;
Jiang, SG ;
Afentoulis, M ;
Baumann, CI ;
Schroeder, DA ;
Olson, SB ;
Wong, MH ;
Fleming, WH .
BLOOD, 2004, 103 (01) :13-19
[4]   Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration [J].
Bhutto, IA ;
McLeod, DS ;
Hasegawa, T ;
Kim, SY ;
Merges, C ;
Tong, P ;
Lutty, GA .
EXPERIMENTAL EYE RESEARCH, 2006, 82 (01) :99-110
[5]   Localization of collagen XVIII and the endostatin portion of collagen XVIII in aged human control eyes and eyes with age-related macular degeneration [J].
Bhutto, IA ;
Kim, SY ;
McLeod, DS ;
Merges, C ;
Fukai, N ;
Olsen, BR ;
Lutty, GA .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (05) :1544-1552
[6]   SDF-1 is both necessary and sufficient to promote proliferative retinopathy [J].
Butler, JM ;
Guthrie, SM ;
Koc, M ;
Afzal, A ;
Caballero, S ;
Brooks, HL ;
Mames, RN ;
Segal, MS ;
Grant, MB ;
Scott, EW .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (01) :86-93
[7]  
Chalasani SH, 2003, J NEUROSCI, V23, P4601
[8]  
Cousins SW, 2002, AGE-RELATED MACULAR DEGENERATION, P27
[9]   CXCR4 receptor expression on human retinal pigment epithelial cells from the blood-retina barrier leads to chemokine secretion and migration in response to stromal cell-derived factor 1α [J].
Crane, IJ ;
Wallace, CA ;
McKillop-Smith, S ;
Forrester, JV .
JOURNAL OF IMMUNOLOGY, 2000, 165 (08) :4372-4378
[10]   Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization [J].
Espinosa-Heidmann, DG ;
Caicedo, A ;
Hernandez, EP ;
Csaky, KG ;
Cousins, SW .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (11) :4914-4919