Proliferative vitreoretinopathy (PVR) is a disease that occurs following rhegmatogenous retinal detachment. It presents most commonly following surgery to reattach the retina. Because of the multitude of cell types and biomolecules that may be involved in PVR and because of the inability to sample the intraocular environment in humans in the early stages of the disease process, it has been difficult to determine which cell type(s) and bioactive molecules (growth factors, cytokines, blood-derived proteins) are most important in the initiation of the disease process. While the etiology of the disease is uncertain, it has been hypothesized that PVR occurs as a result of an intraocular wound healing response in or near the area of the retinal break. In reviewing the data that supports this hypothesis, it is evident that cells of the monocyte/macrophage lineage, cells important in directing the wound healing response in other parts of the body, may play an important and early role in the development of PVR. The experimental work outlined in this proposal is designed to determine the role of circulating monocytes recruited into the eye in the development of PVR in experimental animals. The work relies on the ability to selectively and specifically eliminate circulating monocytes without affecting other leukocytes. By combining this technique with other experiments in which a monocyte-specific chemotactic is employed to selectively recruit monocytes to the eye, it will be possible to determine: 1) if monocytes are necessary for the development of PVR; 2) if monocytes are sufficient for the development of PVR; and 3) what other events in the initiation of the disease are influenced by the monocytes recruited into the eye that become macrophages. The knowledge gained from the completion of this project may allow for the development of an improved animal model of PVR and make it possible to investigate the role of monocyte recruitment in other inflammatory conditions of the eye. It may also suggest potential methods of intervention that would interfere with the initiation of PVR and halt the development of this blinding complication of retinal detachment.
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