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Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration
  1. I A Bhutto,
  2. D S McLeod,
  3. C Merges,
  4. T Hasegawa,
  5. G A Lutty
  1. Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA
  1. Correspondence to: Gerard A Lutty PhD, Wilmer Ophthalmological Institute, 170 Woods Research Building, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-9115, USA; galutty{at}jhmi.edu

Abstract

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.

  • ABC, avidin-biotin complex
  • AMD, age related macular degeneration
  • BLD, basal laminar deposits
  • BM, Bruch’s membrane
  • BSA, bovine serum albumin
  • CC, choriocapillaris
  • CNV, choroidal neovascularisation
  • COPD, chronic obstructive pulmonary disease
  • DET, death to enucleation time
  • DM, diabetes mellitus
  • EPCs, endothelial precursor cells
  • GA, geographic atrophy
  • HSCs, haematopoitic stem cells
  • HTN, hypertension
  • ILM, internal limiting membrane
  • IPM, inner photoreceptor matrix
  • NBT, nitroblue tetrazolium
  • PMT, postmortem time
  • RPE, retinal pigment epithelium
  • SDF-1, stromal cell derived factor 1
  • TBS, TRIS buffered saline
  • VEGF, vascular endothelial growth factor
  • stromal cell derived factor
  • choroid
  • age related macular degeneration
  • choroidal neovascularisation
  • ABC, avidin-biotin complex
  • AMD, age related macular degeneration
  • BLD, basal laminar deposits
  • BM, Bruch’s membrane
  • BSA, bovine serum albumin
  • CC, choriocapillaris
  • CNV, choroidal neovascularisation
  • COPD, chronic obstructive pulmonary disease
  • DET, death to enucleation time
  • DM, diabetes mellitus
  • EPCs, endothelial precursor cells
  • GA, geographic atrophy
  • HSCs, haematopoitic stem cells
  • HTN, hypertension
  • ILM, internal limiting membrane
  • IPM, inner photoreceptor matrix
  • NBT, nitroblue tetrazolium
  • PMT, postmortem time
  • RPE, retinal pigment epithelium
  • SDF-1, stromal cell derived factor 1
  • TBS, TRIS buffered saline
  • VEGF, vascular endothelial growth factor
  • stromal cell derived factor
  • choroid
  • age related macular degeneration
  • choroidal neovascularisation

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Footnotes

  • Competing interests: There are no competing interests.

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