Objective  VEGFA has been proven as a neuroprotective factor and there exists some arguments regarding whether anti-VEGF therapy could injure the neuroretina while resulting in successful inhibition of new vessels. VEGF165 (the predominant isoform of VEGFA) has the same coreceptor NRP-1 with SEMA3A, a proapoptotic agent that has been recently proven. There maybe some competition between VEGF165 and SEMA3A when they combine with NRP-1. We hypothesize that blockade of VEGF164 (VEGF165 in human) may enhance the proapoptotic bioactivity of SEMA3A on the retina in oxygen induced retinopathy (OIR) in rat which is a successful model of retinopathy of prematuity.

Methods The 50/10 OIR model was induced using 50% and 10% oxygen. 100ng VEGF antibody was injected into the vitreous cavity compared with 100ng IgG. Apoptosis was detected by TUNEL procedure while Caspase-3, Bax and Bcl-2 were analyzed by real time PCR. SEMA3A and VEGF164 were observed by real time PCR and Western blotting as well as IF staining of retinal cryosections.

Results There was higher expression of SEMA3A and VEGF164 in 50/10 OIR retinas than the control at the mRNA and protein levels. After intravitreous injection of VEGFab, VEGF164 was successfully blocked. Meanwhile SEMA3A was downregulated.  Alternative aspiration of 50%/10% oxygen aggregated apoptosis in nuclear layers in OIR retinas. But after intravitreous injection of 100ng VEGFab the cell death decreased in the inner nuclear layer, outer nuclear layer and the ganglion cells layer through TUNEL stain. The higher mRNA expression of Bax and Caspase-3 decreased significantly after blockade of VEGF164, which ensured the alleviation of apoptosis in the retina after the VEGFab injection. The tendency of cell death was in accordance with the expression of SEMA3A which was a proapoptotic agent.

Conclusion  VEGF164 possibly regulates the expression of SEMA3A in the retinas of OIR model. The partially intravitreous blocking of VEGF164 doesn’t injure the nuclear cells apparently. The reasoning behind why the apoptosis decrease could be explained by the downregulation of SEMA3A which participates in the neuroprotection of VEGF164 in the retina of OIR rats.