Doctoral Dissertations

Date of Award

12-1997

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Comparative and Experimental Medicine

Major Professor

Barry T. Rouse

Committee Members

Stephen J. Kennel, Robert N. Moore, Leon Potgieter

Abstract

This Ph.D. thesis deals with the pathogenesis and modulation of Herpetic Stromal Keratitis, in the murine model, caused by HSV-1- infection of the cornea.

In the first part of this dissertation, early events in the course of herpetic stromal keratitis are analyzed. The results of in situ hybridization revealed that there is an early induction of proinflammatory molecules following ocular infection by HSV-1 in the stromal cornea. This induction is mainly due to the influx of inflammatory cells. However, the cells infected by HSV-1 were localized exclusively in the corneal epithelium, leading to the hypothesis that there is a physical separation between those cells infected by the virus and those cells producing proinflammatory molecules.

In the second part, the potential efficacy of an expression vector encoding IL-10 was evaluated for its' ability to overcome ocular proinflammatory disease. The results show that this new approach can be applied successfully to assist in the recovery and protection of an animal from specific ocular inflammatory disease. This notion, that an established inflammatory response and disease outcome can be controlled in vivo, opens up new areas of investigation for similar pathologic diseases.

In the third part, the potential use of ocular tissues as a route for immunization was investigated. The data showed that following topical ocular immunization there was induction of mucosal and systemic protective immunity to HSV-1. The protection was accompanied by induction of both humoral and cellular immunity.

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