Model Of Proliferative Vitreoretinopathy Research Articles

Mechanisms Involved in Retinal Pigment Epithelial Cell Chemotaxis

Retinal pigment epithelial (RPE) cell chemotaxis may play an important role in proliferative vitreoretinopathy (PVR). Fibronectin and platelet-derived growth factor are chemoattractants for RPE cells. In this study, we used these chemoattractants to examine mechanisms involved in RPE cell chemotaxis. Our results demonstrate that inhibition of RNA and protein synthesis, but not DNA synthesis, are associated with reduced chemotaxis. Microtubules and microfilaments are involved since cytochalasin B and colchicine are potent inhibitors of RPE cell migration. Dexamethasone, to which a beneficial effect has been attributed in an animal model of PVR, had no effect on RPE cell migration. Information concerning mechanisms involved in RPE cell migration may help to explore new avenues of treatment in PVR.

A refined experimental model for proliferative vitreoretinopathy

Animal models of proliferative vitreoretinopathy (PVR) in which the intact vitreous is injected with large numbers of tissue cultured fibroblasts do not accurately represent the disease as it is found in humans. A refined model of PVR is presented, in which the vitreous is compressed and partially detached using intravitreally injected perfluorpropane, followed by injection of 25,000 homologous fibroblasts. Proliferation occurred on the retinal surface, causing retinal detachments with the same frequency as models using greater numbers of cells.

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 pharmaco kinetic 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.

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.

Proliferative vitreoretinopathy: The rabbit cell injection model for screening of antiproliferative drugs

Injection into the rabbit vitreous of cultured cells results in a condition that mimics some of the features of proliferative Vitreoretinopathy (PVR) in man. Because of its simplicity and reproducibility, this model is especially useful for screening drugs that may control or inhibit intraocular cell proliferation. The cell injection model of PVR is reviewed, and some modifications are described.