AN IN-VIVO MODEL OF HUMAN CYTOMEGALOVIRUS RETINAL INFECTION

PURPOSE: To develop an animal model system in which human retina impla nted in the anterior chamber of the eyes of rats would support human c ytomegalovirus replication. Cytomegalovirus retinitis currently repres ents the most common cause of posterior uveitis in many urban areas in North America. Despite the tremendous interest in cytomegalovirus ret initis as a result of the acquired immunodeficiency syndrome (AIDS) ep idemic, human cytomegalovirus infection has been difficult to model in vivo because of its extreme species-specificity. METHODS: Human retin a was introduced into the anterior chamber of athymic rats and allowed to attach to the rat iris. A human cytomegalovirus mutant carrying a beta-galactosidase indicator gene was then injected into the anterior chamber to infect the implanted tissue. After 4 weeks, the eyes were r emoved, sectioned, and developed with a chromogenic substrate to demon strate the presence and location of beta-galactosidase expression. RES ULTS: Multiple spreading foci of beta-galactosidase expression were fo und in the retinal implants, indicating that human cytomegalovirus rep lication had occurred within the human tissue. There was no infection of rat tissue. CONCLUSIONS: This model allows human cyto megalovirus i nfection of human retina to be established in vivo and sustained long enough to permit multiple cycles of viral replication to occur. The mo del thus has potential for evaluating antiviral therapies directed aga inst human cytomegalovirus retinal disease.