Models for assessing scar tissue inhibitors.
The main purpose of animal models for proliferative vitreoretinopathy (PVR) is to develop pharmacologic therapies for this common cause of blindness. A very large number of pharmacologic agents appear to have potential use in this application by preventing cell proliferation and/or contraction. In practice, however, it has been found that prohibitively extensive numbers of animals and laboratory services are required to establish drug efficacy, safety, and dosage regimes. To lessen this work load and to accelerate drug screening programs, the authors have developed an in vitro model for PVR based on chorioretinal fibroblast growth in three-dimensional collagen lattices. This model yields precise data on the effect of drugs on cell proliferation and contractility. Trifluoperazine, colchicine, 5-fluorouracil, dexamethasone, and penicillamine were screened in this model. The first three agents were found to be inhibitory; on the basis of the pharmacokinetic data, obtained dosage regimes for animal testing were developed. The results obtained are discussed in terms of the in vitro model and the biochemical action of these drugs on the cellular events in PVR. In vitro screening of drugs prior to animal testing offers a significant advance in the quest for a pharmacologic prevention of blindness due to PVR.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control*; D003078:Colchicine / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D010396:Penicillamine / Q000494:pharmacology*; D011817:Rabbits; D012163:Retinal Detachment / Q000517:prevention & control; D012164:Retinal Diseases / Q000473:pathology* / Q000517:prevention & control; D014268:Trifluoperazine / Q000494:pharmacology*; D014822:Vitreous Body / Q000473:pathology
D014268:Trifluoperazine; D003907:Dexamethasone; D003094:Collagen; D004247:DNA; D010396:Penicillamine; D003078:Colchicine; D005472:Fluorouracil