Blanks, Janet C.

The subject invention provides materials and methods useful
in safely and effectively preventing pathological proliferation
of blood vessels. The prevention of the over-proliferation of
blood vessels according to the subject invention is particularly
advantageous for treatment of certain ocular conditions
including age-related macular degeneration (AMD), retinopathy
of prematurity (ROP) and diabetic retinopathy. In
preferred embodiments, the subject invention provides materials
and methods for effective treatment of pathological ocular
neovascularization using gene therapy. In a specific
embodiment the materials and methods of the subject invention
can be used to treat AMD.

Compositions and methods for reducing neovascularization.
Purified nucleic acid constructs and vectors encoding an antiangiogenic
protein operably linked to a GFAP promoter. Vectors
can include at least one hypoxia regulated element,
enhancer element and silencer element. Gene therapy methods
for reducing, delaying or preventing neovascularization
based on the nucleic acid constructs and vectors.

Ocular neovascularization (NV), the development of new blood vessels in the eye, occurs
when excessive vascular endothelial growth factor (VEGF) is produced. Eventually NV
may lead to photoreceptor loss and or blindness, as it does in age-related macular
degeneration (AMD), retinopathy of prematurity (ROP), and diabetic retinopathy.
We tested the hypothesis that the anti-inflammatory cytokine, interleukin-10 (IL-10);
can reduce inflammation and block NV in the affected areas of the retina. The mouse
ROP model was used for this study of NV. Seven day old neonates stayed in 75% oxygen
for five days, then were given intraocular injection of IL-100 and NV was evaluated after
seven days in room air. Controls were uninjected contralateral eyes. IL-l 0 strongly
inhibited NV without affecting intra-retinal vessels. The selective inhibition of IL-10 on NV suggest a possible therapeutic use in infants with ROP, in diabetic retinopathy, and
possibly, in AMD where inflammation is a risk factor.

Age related macular degeneration (AMD) is the leading cause of blindness among the elderly population and oxidative stress induced damage of ocular tissues is thought to play an important role in the etiology of this disease. This current study is aimed at testing pharmacological preconditioning as a possible protective mechanism for retinal cells against oxidative stress induced damage. Since the retinal pigment epithelial (RPE) cells located adjacent to the photoreceptor cells, are believed to be responsible for the initial pathology in AMD we tested our therapy on this cell type. Earlier research conducted with lung cells and in a cardiac model with the nonsteroidal anti-inflammatory drug (NSAID) sulindac (Moench et al., 2009; Marchetti et al., 2009) indicate that sulindac can protect normal cells from oxidative damage through ischemic preconditioning (IPC) pathways. This led us to test whether sulindac can also protect significant protection against both tert-butyl hydrogen peroxide (TBHP) induced chemical stress and UVB light induced photooxidative damage through a preconditioning mechanism.