Traction retinal detachment is a major cause of blindness and occurs in a variety of conditions including trauma, diabetes, and other vascular conditions characterized by cellular proliferation. Vitreoretinal traction caused by massive periretinal proliferation (MPP), now proliferative vitreoretinopathy (PVR), is the leading cause of failure of surgery for rhegmatogenous retinal detachment; PVR is the result of continued proliferation of cells that exert new tractional forces within the eye. Many blinding conditions share the basic wound-healing response of cellular proliferation followed by cell contraction leading to traction retinal detachment. We have modified and developed a model of PVR in the rabbit. We now propose to investigate in the rabbit eye a series of drugs to follow the observations of other research related to steroids and 5-fluorouracil, as effective drugs for the prevention of PVR. Daunomycin was identified as a likely candidate and will be studied in detail by standard pharmacologic procedures (dose-response curves, retinotoxicity, pharmacokinetics and metabolism, effectiveness in combination with vitrectomy). Other cytotoxic drugs will be screened for effectiveness, first in in vitro, then in in vivo experiments. The most efficacious drugs will be evaluated in the manner outlined for daunomycin.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004909-03
Application #
3259518
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
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
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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