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Fall 2011
Newsletter

TODD P. MARGOLIS, M.D., Ph.D.

Professor of Ophthalmology and Physiology
 


Research Summary

Infectious and Inflammatory Ocular Diseases

My clinical experience is in the medical and surgical management of infectious and inflammatory ocular disease. I have a particular interest in ocular disease due to the herpes viruses. My clinical research is aimed at understanding the pathogenic mechanisms leading to atypical presentations of ocular infections. This work dovetails closely with my laboratory research, providing valuable clinical samples and raising important questions that can be addressed at the laboratory bench.

Cellular Studies of HSV.
The primary focus of my laboratory research is to carry out studies on the cellular and molecular mechanisms that regulate the establishment and maintenance of latent neuronal infection with herpes simplex virus (HSV). Ongoing research is aimed at documenting the role of neuronal gene expression in the establishment and maintenance of HSV latency. In addition, we are studying the role of the host immune system and the sympathetic nervous system in regulating these processes.

In related research, I have collaborated on studies aimed at understanding regulation of the HSV LAT promoter during latent infection. The ultimate goal of this work is to gain enough understanding of the regulation of latent infection with herpes simplex virus that it may be possible to devise therapeutic interventions that prevent reactivation of the virus from the latent state.

Diagnostic PCR Assays.
A second line of investigation involves the development of polymerase chain reaction (PCR) based assays for the diagnosis of infectious retinitis. We have now completed assays for the detection of HSV, varicella zoster virus and cytomegalovirus (CMV) retinitis, using vitreous as a substrate. All three assays are rapid, make no use of radioactive reagents, and are relatively inexpensive to run. In addition they are highly sensitive and specific. Current work is aimed at developing similar assays using aqueous as a substrate.

CMV Retinitis Studies.
A third line of investigation focuses on blinding CMV retinitis in patients with AIDS - specifically, studies aimed at determining the molecular basis of antiviral drug resistance by CMV and the role of strain-specific determinants of glycoprotein B in the pathogenesis of CMV retinitis. Since the virus is extremely difficult to grow from the eye, we use molecular techniques to amplify CMV genes of interest directly from the vitreous of patients with active CMV retinitis. The amplified genes are then analyzed in order to identify DNA polymorphisms associated with antiviral drug resistance or specific viral strains.
We're also examining the role of the medicine in the diagnosis and management of patients with CMV retinitis. Finally, we are studying novel presentation of CMV keratitis and iritis in otherwise healthy individuals.

VSV Ocular Disease.
We are currently studying and describing previously unrecognized presentations of VSV ocular disease, work aided by the use of molecular diagnostics.


 

 

©2011 University of California, San Francisco, Department of Ophthalmology
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