Our studies of various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment comprise four areas: (1) coronavirus infection in ocular and optic nerve cells; (2) the possible roles of viruses in human diseases; (3) molecular diagnosis and pathogenesi of cytomegalovirus (CMV) infections in humans, and (4) Varicella - zoster virus infections of the retina. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Ini al retinal damage is followed by clearance of infectious virus and progressive retinal degeneration. In situ hybridization techniques identified that the viral RNA persists within the M?ller cells and RPE cells throughout the course of the disease. Recent studies show that there are genetic and immunologic components to this disease. The retinal degenerative pathologi manifestations of the disease can be influenced by the genetics of the host That is, some strains of mice are resistant to virus-induced retinal degenerative changes. The pathologic changes are also closely related to the development of anti-retinal and anti-RPE antibodies. These findings suggest a role for autoimmunity in the pathogenesis. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. Human CMV is a herpesvirus that is a major cause of blindness in children born with congenital infections and in immunocompromised individuals. It is difficult to study CMV latency in man. Therefore cell culture models of CMV replication and latency may provide insight into a rationale for alternative treatment modalities. We identified that CMV replicates in hum RPE cells. Virus replication is extremely slow and is associated with a lo expression of IE viral proteins. These may be critical variables in viral persistence and viral activation within the retina.
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