During the past year we have initiated studies to evaluate the various virologic and immunopathologic processes which occur when viruses replicate in the ocular microenvironment. This is a new project which is composed of three areas: (1) Evaluation of virus spread in HSV-1 induced retinitis. (2) Studies on coronavirus infection in ocular and optic nerve cells. (3) Determination of possible role of other viruses in human eye diseases. Retinitis following anterior chamber inoculation of herpes simplex virus (HSv-1) is an interesting model of viral spread and virus induced disease. During the past year we have elucidated some of the pathologic mechanisms involved in this disease. We found that footprints of the immune system (IFN-gamma and MHC class II antigen expression) can be identified in the protected retina strongly indicating that it is the immune system which protects the retina from virus destruction. Moreover, we identified the virus in the capillary body and ciliary nerves suggesting that this may be the mode of spread of the virus to the uninjected eye. Elucidation of virus spread and activation in the retina may provide insight into these same mechanisms in human disease, such as acute retinal necrosis. We have initiated studies to evaluate coronavirus infections in the eye and optic nerve. Monoclonal anti-virus receptor antibody has identified selected cells within the eye which express virus receptors. Preliminary studies indicate that the virus is capable of inducing ocular damage in the posterior pole.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000240-03
Application #
3918836
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1988
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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