The goal of the proposed research is to develop a pharmacologic therapy for the prevention of proliferative vitreoretinopathy (PVR), the most common cause of failure of retinal detachment surgery. In the past grant period we have screened drugs for efficacy in rabbit model of PVR. Daunomycin proved to be the drug of choice and is currently undergoing clinical trail in Europe. However, the therapeutic window of daunomycin is narrow. Additional research is necessary to provide improved drug delivery and to increase efficacy through combination with other drugs. The pathogenesis of PVR involves a sequence of wound healing processing gone awry, each of which is a target for intervention. Thus suppression of post-surgical inflammation, blood-ocular barrier breakdown and attraction and migration of cells into the vitreous by anti-inflammatory and anti-chemotactic agents in combination with daunomycin could increase its efficacy and reduce its toxicity. The proposed studies will evaluate combinations of anti- inflammatory and anti-chemotactic drugs with daunomycin in rabbit models of PVR characterized by a strong inflammatory or chemotactic response. The toxicity of the most efficacious combination will be evaluated in primates. The results of these studies is of importance for the rational design of effective pharmacologic prevention of PVR in man.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004909-05
Application #
3259519
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Wong, C G; Naripthaphan, P; Renardel de Lavalette, V (1987) Ornithine decarboxylase activity in rabbit retina following treatment with alpha-difluoromethylornithine. Biochem Pharmacol 36:4325-9
Renardel de Lavalette, V W; Miller, B; Wong, C G et al. (1986) Ornithine decarboxylase activity during formation of experimental epiretinal membranes. Curr Eye Res 5:101-4
Verdoorn, C; Renardel de Lavalette, V W; Dalma-Weizhausz, J et al. (1986) Cellular migration, proliferation, and contraction. An in vitro approach to a clinical problem--proliferative vitreoretinopathy. Arch Ophthalmol 104:1216-9
Orr, G; Goodnight, R; Lean, J S (1986) Relative permeability of retina and retinal pigment epithelium to the diffusion of tritiated water from vitreous to choroid. Arch Ophthalmol 104:1678-80
Orr, G; Tervaert, D C; Lean, J S (1986) Aqueous concentrations of fluorouracil after intravitreal injection. Normal, vitrectomized, and silicone-filled eyes. Arch Ophthalmol 104:431-4
Wong, C; Ishibashi, T; Tucker, G et al. (1985) Responses of the pigmented rabbit retina to NMPTP, a chemical inducer of parkinsonism. Exp Eye Res 40:509-19
Wong, C G; Gee, E; Ryan, S J (1985) Consequences of ornithine decarboxylase inactivation by alpha-difluoromethylornithine and 5-fluorouracil on the growth of rabbit fibroblasts. Curr Eye Res 4:843-6