The first demonstration that VEGF was required for retinal neovascularization (phase II of ROP) came from studies of the mouse model of proliferative retinopathy . The location and time course of VEGF expression in association with retinal neovascularization was found to correlate with disease in the mouse ROP model. After oxygen-induction of vessel loss and subsequent hypoxia, there is an increase in the expression of VEGF mRNA in the retina within 12 h. The increased expression is sustained until the development of neovascularization [55, 67]. This occurs in the ganglion cell layer and in the inner nuclear layer consistent with expression in astrocytes and Muller cells.
To establish that a growth factor is critical for neovascularization, inhibition of the factor must inhibit the proliferation of blood vessels. Inhibition of VEGF with intravitreal injections of either an anti-VEGF antisense oligonu-
cleotide or with a molecule to adsorb VEGF (VEGF receptor/IgG chimera) significantly decreased the neovascular response in the mouse model of ROP [6,61], indicating that VEGF is a critical factor in retinal neovascularization. VEGF also has been associated with ocular neo-vascularization by other investigators in other animal models, confirming the central role of VEGF in neovascular eye disease [3,18, 47, 72, 76]. These results correspond to what is seen clinically. VEGF is elevated in the vitreous of patients with retinal neovascularization [2, 4]. VEGF was found in the retina of a patient with ROP in a pattern consistent with mouse results . Based on these and other studies an anti-VEGF aptamer is now available to treat neovas-cularization associated with age-related macular degeneration and is in phase III clinical trials for diabetic retinopathy. Clinical trials are planned for evaluation of treatment of the pro-liferative phase of ROP with anti-VEGF injections.
• VEGF is an important factor for the development of retinal vascular proliferation in ROP. Inhibition of VEGF with anti VEGF treatment (Anti-VEGF aptamer or anti-VEGF antibody) has been successfully used clinically in other proliferative retinal vascular diseases such as age-related macular degeneration and diabetic retinopathy. Clinical trials are in the planning stage for anti-VEGF therapy for ROP (injection into the vitreous in phase II) to prevent retinal detachment and blindness
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