Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity
AUTOR(ES)
Shih, Shu-Ching
FONTE
American Society for Clinical Investigation
RESUMO
Oxygen administration to immature neonates suppresses VEGF-A expression in the retina, resulting in the catastrophic vessel loss that initiates retinopathy of prematurity. To investigate the mechanisms responsible for survival of blood vessels in the developing retina, we characterized two VEGF-A receptors, VEGF receptor–1 (VEGFR-1, also known as Flt-1) and VEGF receptor–2 (VEGFR-2, also known as Flk-1). Surprisingly, these two VEGF-A receptors differed markedly during normal retinal development in mice. At 5 days postpartum (P5), VEGFR-1 protein was colocalized with retinal vessels, whereas VEGFR-2 was detected only in the neural retina. Real-time RT-PCR identified a 60-fold induction of VEGFR-1 mRNA in retina from P3 (early vascularization) to P26 (fully vascularized), and no significant change in VEGFR-2 mRNA expression. Placental growth factor-1 (PlGF-1), which exclusively binds VEGFR-1, decreased hyperoxia-induced retinal vaso-obliteration from 22.2% to 5.1%, whereas VEGF-E, which exclusively binds VEGFR-2, had no effect on blood vessel survival. Importantly, under the same conditions, PlGF-1 did not increase vasoproliferation during (a) normal vessel growth, (b) revascularization following hyperoxia-induced ischemia, or (c) the vasoproliferative phase, indicating a selective function supporting blood vessel survival. We conclude that VEGFR-1 is critical in maintaining the vasculature of the neonatal retina, and that activation of VEGFR-1 by PlGF-1 is a selective strategy for preventing oxygen-induced retinal ischemia without provoking retinal neovascularization.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=162289Documentos Relacionados
- Oxygen-induced genetic changes in dry yeast cells.
- Singlet oxygen-induced mutations in M13 lacZ phage DNA.
- STUDIES ON THE MECHANISM OF OXYGEN-INDUCED HYPOVENTILATION. AN EXPERIMENTAL APPROACH*
- The role of endotoxin in protection of adult rats from oxygen-induced lung toxicity.
- An oxygen-induced but protein F-independent fibronectin-binding pathway in Streptococcus pyogenes.