Objective:To investigate the effects of hypoxia inducible factor-1α(HIF-1α)antisense oligonucleotides(ASODN)on the expression of vascular endothelial growth factor(VEGF)and retinal neovascularization in premature rat with retinopathy.Methods:A total of 80 postnatal day 7 wistar rats were randomly assigned into two group.The experimental group(n=40)were established as ROP mode group.The control group(n=40)was exposed to room air in the same experimental condition.HIF-1αASODN was injected into rats’left cavum vitreum at 12、14、16 d in these two groups.Some of the experimental group were injected with saline at 14、16 d.So there were five groups of specimens including:normal eye(A)

normal eye with HIF-1αASODN(A1)

ROP eye(B)

ROP eye with HIF-1α ASODN(B1)

ROP eye+saline(B2).The retinal vascular development and proliferation in five groups were evaluated by the retina stretch preparation of 15 newborn rats at 12、14、17 d respectively.Eyeball cross-section was staimed with hematoxylin and eosin(HE).The nuclei of proliferative retinal vessels of five groups were counted.The expression of VEGF and HIF-1αin retina by immunohisto-chemical stain were observed among all groups.Results:In ROP group(B)the central vessels became tortuous and constricted and the central avascular area increased at 12 d.At 14 d

neovascularization was seen

peaking at 17 d.ROP eye with HIF-1αASODN(B1)presented the same as group A

but Neovascularization decreased obviously as compcured with group B.Retinal vessel shape of ROP eye+saline(B2)is same as group B.VEGF was mainly expressed in capillary endothelium endochylema and nucleus of ganglionic layer of retina and inner nuclear layer.The expressions of VEGF were weaker in group A

A1 than in group B

B2

with significant differences(P<0.05).The expression of HIF-1αwas mainly seen in capillary endothe lium nucleus of ganglionic layer of retina and inner nuclear layer.No HIF-1αwere observed in group A and A1.The expressions of HIF-1αwere weaker in group B1 than in group B and B2

with significant difference(sP<0.05).Conclusion:Breathing in homo-concentration oxygen then stopping oxygen supply suddenly can increase expression of HIF-1αand VEGF in rat’s retina.The positive correlation is presented between them.Injecting HIF-1αASODN into rat’s left cavum vitreum can inhibit expression of HIF-1αand VEGF in retina

thereby inhibit retinal neovascularization.HIF-1αmight be one of the targets for the gene therapy for ROP.