During the past year, we have studied various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment. This project consists of three areas: (1) studies on coronavirus infection in ocular and optic nerve cells; (2) determination of the possible roles of viruses in human diseases; (3) antiviral therapeutic actions of cytokines and drugs. We have established that murine coronavirus can induce ocular disease and thus may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild inflammation. The initial retinal damage is followed by clearance of the virus and progressive retinal destruction, even months after the virus is gone. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. The need for effective drug treatment and prevention of herpes virus and other viral diseases has assumed growing importance. We found that leukoregulin, a naturally occurring immunologic cytokine, increases the antiviral actions of the drug acyclovir. These findings which demonstrate that combination immunotherapy and chemotherapy can produce substantial inhibition of herpes virus replication, provide a rationale for the application of this approach to the treatment of virus infections.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000240-04
Application #
3877060
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Hayashi, Kozaburo; Hooper, Laura C; Detrick, Barbara et al. (2009) HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9. Arch Virol 154:219-26
Forooghian, Farzin; Macdonald, Ian M; Heckenlively, John R et al. (2008) The need for standardization of antiretinal antibody detection and measurement. Am J Ophthalmol 146:489-95
Hayashi, Kozaburo; Hooper, Laura C; Chin, Marian S et al. (2006) Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1-human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors. J Gen Virol 87:2161-9
Hooks, John J; Chin, Marian S; Srinivasan, Kumar et al. (2006) Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway. Microbes Infect 8:2236-44
Djalilian, Ali R; Nagineni, Chandrasekharam N; Mahesh, Sankanaranayana P et al. (2006) Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin. Cornea 25:709-14
Chin, Marian S; Caruso, Rafael C; Detrick, Barbara et al. (2006) Autoantibodies to p75/LEDGF, a cell survival factor, found in patients with atypical retinal degeneration. J Autoimmun 27:17-27
Hooper, Laura C; Chin, Marian S; Detrick, Barbara et al. (2005) Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-alpha, soluble TNFR2 and altered TNF-alpha signaling. J Neuroimmunol 166:65-74
Hooks, John J; Wang, Yun; Detrick, Barbara (2003) The critical role of IFN-gamma in experimental coronavirus retinopathy. Invest Ophthalmol Vis Sci 44:3402-8
Momma, Yuko; Nagineni, Chandrasekharam N; Chin, Marian S et al. (2003) Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus. Invest Ophthalmol Vis Sci 44:2026-33
Hooks, J J; Tso, M O; Detrick, B (2001) Retinopathies associated with antiretinal antibodies. Clin Diagn Lab Immunol 8:853-8

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