Herpes simplex keratitis (HSK) is a major problem of epidemic proportions, in spite of the fact that many excellent antiviral drugs exist for treatment of episodes of active HSK. It is clear that both viral and host immune factors collaborate to determine the eventual course of disease expression in any individual with HSK. Unfortunately, huge gaps exist in our understanding of the cellular and molecular events underlying the progression of a corneal epithelial infection with herpes to more devastating corneal stromal disease. We have discovered, using inbred congenic strains of mice, genetically-linked controls which govern the development of HSK which is either predominantly epithelial or predominantly stromal. We have mapped the phenomenon to genes linked to the Igh locus on chromosome XII. Furthermore, in preliminary experiments we have already shown that we can modify the course of disease in those animals which are typically susceptible to the most severe keratitis, through immunologic strategies, so that little to no keratitis at all develops after herpes corneal infection. We propose in this application to study this phenomenon in more detail, with the expectation that understanding it at a cellular and molecular level will enable us to design therapeutic strategies which could modify not only the degree of corneal disease developing after herpes infection, but also the development or continuation of latent infection in the trigeminal ganglion. We plan to study the role of helper T cells, cytotoxic T cells, suppressor T cells, and specific antiherpes antibody and their respective roles in both the protection from pathology and establishment of ganglionic latency, and in the production of pathology and facilitation of latency establishment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006008-03
Application #
3261916
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1985-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Pedroza-Seres, M; Goei, S; Merayo-Lloves, J et al. (1995) T cell receptor V beta gene expression in experimental herpes stromal keratitis. Eye (Lond) 9 ( Pt 5):599-604
Heiligenhaus, A; Wells, P A; Foster, C S (1995) Immunisation against HSV-1 keratitis with a synthetic gD peptide. Eye (Lond) 9 ( Pt 1):89-95
Tamesis, R R; Messmer, E M; Rice, B A et al. (1994) The role of natural killer cells in the development of herpes simplex virus type 1 induced stromal keratitis in mice. Eye (Lond) 8 ( Pt 3):298-306