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An in vivo model of human cytomegalovirus retinal infection
K A Laycock1, E D Fenoglio, K K Hook
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Purpose:
To develop an animal model system in which human retina implanted in the anterior chamber of the eyes of rats would support human cytomegalovirus replication. Cytomegalovirus retinitis currently represents the most common cause of posterior uveitis in many urban areas in North America. Despite the tremendous interest in cytomegalovirus retinitis as a result of the acquired immunodeficiency syndrome (AIDS) epidemic, human cytomegalovirus infection has been difficult to model in vivo because of its extreme species-specificity.
Methods:
Human retina 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 removed, sectioned, and developed with a chromogenic substrate to demonstrate the presence and location of beta-galactosidase expression.
Results:
Multiple spreading foci of beta-galactosidase expression were found in the retinal implants, indicating that human cytomegalovirus replication had occurred within the human tissue. There was no infection of rat tissue.
Conclusions:
This model allows human cytomegalovirus infection of human retina to be established in vivo and sustained long enough to permit multiple cycles of viral replication to occur. The model thus has potential for evaluating antiviral therapies directed against human cytomegalovirus retinal disease.