Supplemental oxygen is necessary for normal lung development in premature neonates, but oxygen also suppresses VEGF-A expression in the retina, causing retinal vessel damage and retinopathy of prematurity (ROP). The mechanisms responsible for survival of blood vessels in the developing retina have been unclear, but in the July 1 Journal of Clinical Investigation, Shu-Ching Shih and colleagues at Harvard Medical School and Children's Hospital Boston show that selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in ROP (Journal of Clinical Investigation, 112:50–57, July 1, 2003).

Shih et al. examined the expression of two VEGF-A receptors, VEGFR-1 (also known as Flt-1) and VEGFR-2 (also known as Flk-1), during normal retinal development in mice. They observed that at 5 days postpartum, VEGFR-1 was colocalized with retinal vessels, whereas VEGFR-2 was detected only in the neural retina. In addition, they used placental growth factor-1 (PlGF-1), which exclusively binds VEGFR-1, and showed that specific activation of VEGFR-1, but not VEGFR-2, protected against oxygen-induced vessel loss without stimulating vascular proliferation and neovascularization in vivo.

"Activation of VEGFR-1 by PlGF-1 is a selective strategy for preventing oxygen-induced retinal ischemia without provoking retinal neovascularization," conclude the authors.

"ROP is different from other pathologies of abnormal vessel regression in that the vessels eliminated are immature and hence VEGF dependent. Immaturity of vessels in expanding tumors may also be exploited for enforcing vessel regression via a VEGF withdrawal strategy. There are no clues, however, on how the rarefaction of mature vessels that are refractory to VEGF might be prevented," writes Eli Keshet from The Hebrew University—Hadassah Medical School in an accompanying commentary.