Herpetic Stromal Keratitis (HSK) is an immunoinflammatory lesion of the cornea set off by herpes simplex virus (HSV) infection. This important cause of human blindness can be conveniently studied in mouse model systems where it has been shown that lesions are the consequence of a complex multistep process involving numerous molecular and cellular participants. The proposed research is designed to identify molecular signals that result from HSV infection of the corneal epithelium which cause rapid inflammatory changes in the underlying stroma. These include neutrophil infiltration and angiogenesis. The molecular signals are hypothesized to be multiple and include cytokines, chemokines, stress proteins, and fragments of viral DNA that are bioactive. The clinical and progressive phase of HSK depends on stimulation of CD4+ T cells which are hypothesized to enter the cornea once sufficient neovascularization has occurred. The research seeks to determine the mechanism by which CD4+ T cells are activated to contribute to tissue damage. Experiments are designed to define the respective roles of viral antigen specific and nonviral specific mechanisms of activation. Investigations also focus on angiogenesis during clinical HSK and the relevance of therapies designed to inhibit neovascularization.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005093-22
Application #
6949912
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Shen, Grace L
Project Start
1984-09-30
Project End
2007-09-29
Budget Start
2005-09-30
Budget End
2006-09-29
Support Year
22
Fiscal Year
2005
Total Cost
$355,940
Indirect Cost
Name
University of Tennessee Knoxville
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
003387891
City
Knoxville
State
TN
Country
United States
Zip Code
37996
Rajasagi, Naveen K; Rouse, Barry T (2018) Application of our understanding of pathogenesis of herpetic stromal keratitis for novel therapy. Microbes Infect 20:526-530
Bhela, Siddheshvar; Rouse, Barry T (2018) Are miRNAs critical determinants in herpes simplex virus pathogenesis? Microbes Infect 20:461-465
Sehrawat, Sharvan; Kumar, Dhaneshwar; Rouse, Barry T (2018) Herpesviruses: Harmonious Pathogens but Relevant Cofactors in Other Diseases? Front Cell Infect Microbiol 8:177
Varanasi, Siva Karthik; Rajasagi, Naveen K; Jaggi, Ujjaldeep et al. (2018) Role of IL-18 induced Amphiregulin expression on virus induced ocular lesions. Mucosal Immunol 11:1705-1715
Rajasagi, Naveen K; Bhela, Siddheshvar; Varanasi, Siva Karthik et al. (2017) Frontline Science: Aspirin-triggered resolvin D1 controls herpes simplex virus-induced corneal immunopathology. J Leukoc Biol 102:1159-1171
Varanasi, Siva Karthik; Reddy, Pradeep B J; Bhela, Siddheshvar et al. (2017) Azacytidine Treatment Inhibits the Progression of Herpes Stromal Keratitis by Enhancing Regulatory T Cell Function. J Virol 91:
Varanasi, Siva Karthik; Donohoe, Dallas; Jaggi, Ujjaldeep et al. (2017) Manipulating Glucose Metabolism during Different Stages of Viral Pathogenesis Can Have either Detrimental or Beneficial Effects. J Immunol 199:1748-1761
Bhela, Siddheshvar; Varanasi, Siva Karthik; Jaggi, Ujjaldeep et al. (2017) The Plasticity and Stability of Regulatory T Cells during Viral-Induced Inflammatory Lesions. J Immunol 199:1342-1352
Gimenez, Fernanda; Bhela, Siddheshvar; Dogra, Pranay et al. (2016) The inflammasome NLRP3 plays a protective role against a viral immunopathological lesion. J Leukoc Biol 99:647-57
Rajasagi, Naveen K; Rouse, Barry T (2016) IL-2 complex treatment amplifies CD8+ T cell mediated immunity following herpes simplex virus-1 infection. Microbes Infect 18:735-746

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