Original Article Role of hypoxia-inducible factor-1α and survivin in oxygen-induced retinopathy in mice

Survivin, an inhibitor of apoptosis protein family, appears to be involved in tumor progression and angio- genesis. The current study contains rare reports on the transcriptional regulation of survivin expression in retinal neovascularization (NV). The aim of this study was to investigate hypoxia-inducible factor-1α (HIF-1α) and survivin expression in pathologic ocular angiogenesis and to determine their correlation and cellular location. The model of oxygen-induced retinopathy (OIR) was induced in C57BL/6 mice by exposing 75% oxygen from postnatal day 7 (p7) to p12 and then followed by room air. Fluorescence angiography, immunostaining and HE staining were used to assess the visualization of retinal vascularization and the expression of HIF-1α and survivin protein in retina oxygen-induced retinopathy was characterized by clusters of neovascularization and regions of non-perfusion. HIF- 1α and survivin were both highly expressed in OIR and a positive correlation existed between HIF-1α and survivin expression. In OIR, there was more HIF1-α protein expression in the inner nuclear layer (INL), the ganglion cell layer (GCL), and more neovascularization breaking through the inner retina and survivin protein was detected in GCL, and more neovascularization breaking through the inner retina. Our study had shown that both HIF1-α and survivin are involved in the retinal neovaccularization. Meanwhile HIF1-α and survivin have differential cellular location in retinal ischemia, and HIF1-α might be a critical transcription factor involved in the regulation of survivin expression.