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Endothelial cell proliferation in the choriocapillaris during human retinal differentiation
  1. A Allende1,
  2. M C Madigan1,
  3. J M Provis2
  1. 1Discipline of Clinical Ophthalmology and Save Sight Institute, University of Sydney, NSW 2006, Australia
  2. 2ARC Centre of Excellence in Visual Science, Research School of Biological Sciences, The Australian National University, GPO 475, Canberra, ACT 2601, Australia
  1. Correspondence to: Alexandra Allende Discipline of Clinical Ophthalmology and Save Sight Institute, University of Sydney, GPO 4337, Sydney, NSW 2001, Australia; alexa{at}med.usyd.edu.au

Abstract

Background: Differentiation patterns of the neural retina and its retinal vasculature are not well matched. The foveal region differentiates first, however the central retina is not vascularised until late in gestation. The authors explored the hypothesis that higher rates of endothelial cell proliferation in the choriocapillaris of the central retina might compensate for the slow growth of central retinal vessels, providing supplementary nutrients to the region during the early stages of neuronal maturation.

Methods: Frozen sections of five human fetal eyes (14–18.5 weeks’ gestation), were examined for Ki-67 and CD34 immunoreactivity using confocal microscopy. Measurements of choriocapillaris area and the number of proliferating choroidal endothelial cells were used to calculate the rate of choroidal endothelial proliferation at five different chorioretinal locations.

Results: The choriocapillaris area is consistently greater in the foveal region than at other locations and increases progressively with age. A higher rate of endothelial cell proliferation was found in parts of the choriocapillaris associated with the undifferentiated (proliferating) neural retina, compared with the differentiated, central region.

Conclusion: The findings suggest that mechanisms regulating proliferation and growth of the choroidal vasculature are independent of differentiation in the neural retina, and are thus profoundly different from mechanisms that regulate formation of the retinal vasculature.

  • BMSC, bone marrow stromal cells
  • EC, endothelial cells
  • F, foveal
  • FGF, fibroblast growth factor
  • GCL, ganglion cell layer
  • HIF1-α, hypoxia inducible factor-1alpha
  • IR, immunoreactive
  • N, nasal
  • NFL, nerve fibre layer
  • phosphate buffered saline
  • BS, PBS
  • RPE, retinal pigmented epithelium
  • T, temporal
  • VEGF, vascular endothelial growth factor
  • choroid
  • retinal development
  • angiogenesis
  • primates
  • BMSC, bone marrow stromal cells
  • EC, endothelial cells
  • F, foveal
  • FGF, fibroblast growth factor
  • GCL, ganglion cell layer
  • HIF1-α, hypoxia inducible factor-1alpha
  • IR, immunoreactive
  • N, nasal
  • NFL, nerve fibre layer
  • phosphate buffered saline
  • BS, PBS
  • RPE, retinal pigmented epithelium
  • T, temporal
  • VEGF, vascular endothelial growth factor
  • choroid
  • retinal development
  • angiogenesis
  • primates

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