Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity

Jonathan Stone*, Tailoi Chan-Ling, Jacob Pe'er, Ahuva Itin, Hadassah Gnessin, Eli Keshet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

Abstract

Purpose: To assess the role of vascular endothelial growth factor (VEGF) in the feline model of retinopathy of prematurity (ROP). Methods. Retinopathy of prematurity was induced in neonatal cats by raising them in an oxygen-enriched (70% to 80%) atmosphere for 4 days to suppress vessel formation and then returning them to room air for 3 to 27 days. In situ hybridization was used to detect the expression of VEGF and its high-affinity receptor, flk-1, in the retina of neonatal cats, and glial fibrillary acidic protein immunocytochemistry was used to assess astrocyte status. Results. The expression of VEGF in the innermost layers of retina fell in hyperoxia and increased on return to room air. Vascular endothelial growth factor expression was transient; it was maximal where vessels were about to form, and it rapidly downregulated after vessels had formed. During the proliferative vasculopathy of ROP, VEGF expression was stronger than in the normally developing retina, and the astrocytes that normally express VEGF degenerated. After the degeneration of astrocytes, VEGF was expressed by neurones of the ganglion cell layer. flk-1 was expressed by intraretinal and preretinal vessels. Supplemental oxygen therapy reduced or eliminated the overexprression of VEGF expression, astrocyte degeneration, and formation of preretinal vessels. Conclusions. Regulation of VEGF by tissue oxygen mediates the inhibition of vessel growth during hyperoxia and the subsequent proliferative vasculopathy. Degeneration of retinal astrocytes creates conditions for the growth of preretinal vessels.

Original languageEnglish
Pages (from-to)290-299
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number2
StatePublished - Feb 1996

Keywords

  • astrocytes
  • retinal development
  • retinal vasculature
  • retinopathy of prematurity
  • vascular endothelial growth factor (VEGF)

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