New strategies for treating NV

ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY 

In addition to the work presented here, several alternative viral-vectored approaches have been reported recently. An adeno-associated viral vector (AAV) encoding the soluble VEGF receptor 1, sFlt-1, shows promise for long-term inhibition of two types of ocular neovascularization (Lai et al., 2002). This vector, when injected into the anterior chamber, resulted in expression in both the corneal endothelium and iris pigment epithelium and reduced corneal NV by 36%. Subretinal injection of the same vector reduced choroidal NV subsequent to laser lesions around the optic nerve. These results suggest that a secretable factor expressed in one or more transduced cell populations can be elfective in the control of ocular NV occurring in a disparate cell population. 

first purified from human retinal pigment epithelial cultures as a factor that induces neuronal differentiation of cultured retinoblastoma cells (Tombran-Tink et al., 1991 Steele et al., 1993), has been recently shown to regulate normal angiogenesis in the eye (Dawson et al., 1999). PEDF is found both intracellularly and extracellularly in the fetal and early adult eye but is lost at the onset of senescence (Becerra, 1997 Araki et al., 1998). It is down-regulated by hypoxia and induced in the retina as a result of 

Although the minimum effective intraocular dose of PEDF or K1K3 for controlling ischemic retinopathy is unknown, previous studies following systemic administration of PEDF protein in the same model we employ here suggest that the therapeutic threshold is approximately 5-11 /ig/day (Stellmach et al., 2001) by I.P. administration. If we make the simplest and most conservative 

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