Establishing an Animal Model of Cytomegalovirus Keratouveitis in Rats: Broad Infection of Anterior Segment Tissue by Cytomegalovirus

PURPOSE: Considering the difficulty of obtaining adequate biological tissue in clinical practice, we established an animal model of cytomegalovirus (CMV) keratouveitis in rats and investigated the viral infection sites and corresponding imaging and histopathological features. METHODS: Subconjunctival injection and topical use of dexamethasone were used to induce ocular immunosuppression in rats followed by intracameral inoculation of murine cytomegalovirus (MCMV). The clinical manifestations, intraocular pressure (IOP) and imaging changes were observed. Infected eyes were further examined by immunofluorescence, light microscopy, and electron microscopy. MCMV RNA was detected by reverse transcription-polymerase chain reaction. RESULTS: Typical keratouveitis occurred in the experimental rats and was characterized by corneal edema, keratic precipitates, and iridocyclitis with increased IOP. Corneal endothelial lesions displayed as “black holes,” enlarged intercellular gaps, and high-intensity cellular infiltration by confocal microscopy, consistent with the pathological changes of “ballooning degeneration,” endothelial cell detachment, and inflammatory cell infiltration. Mitochondrial edema was the most prominent organelle lesion in endothelial cells. Trabeculitis, mechanical obstruction of Schlemm's canal, and anterior chamber angle stenosis accounted for elevated IOP. Inflammation of the iris and ciliary body tended to transform into a chronic form. Immunofluorescence revealed that corneal endothelial cells, iris cells, trabecular meshwork cells, and monocytes could be infected by MCMV. MCMV RNA was found in the anterior segments after infection. CONCLUSIONS: CMV can widely infect anterior segment tissue, including the corneal endothelium, iris, and trabecular meshwork, in vivo, inducing the corresponding clinical manifestations. Corneal endotheliitis and hypertensive anterior uveitis could be the specific stage of anterior segment infection of CMV.