The pathogenic mechanism for herpetic chorioretinitis in the neonate is poorly understood. Our preliminary studies in the newborn rabbit revealed that a) mononuclear cells infected with type 2 herpes simplex virus (HSV-2), rather than free HSV-2, produce retinochoroiditis; b) HSV-2 induced Fc receptors for normal IgG on mononuclear cells; and c) mononuclear cells infected with HSV-2 required normal IgG for the induction of the ocular lesion in the newborn rabbits. Based on these observations, as well as those of other researchers, the following pathogenic process for the development of retinochoroiditis in the neonate is proposed: Following infection, HSV-2 induces Fc receptors for normal IgG on the mononuclear cells. The binding of IgG to the Fc receptors changes the nature of the cell surface of HSV-infected mononuclear cells and leads to the entrapment of the cell in the capillaries of the retina and choroid. The entrapped HSV-infected mononuclear cell then initiates infection at the site and produces retinochoroiditis. To examine the validity of this proposed pathogenic process, the following series of experiments will be carried out: a) subpopulations of mononuclear cells which are major carriers of HSV-2 and are capable of producing retinochoroiditis in the newborn rabbits will be determined; b) the interaction between HSV-2 and mononuclear cells will be studied, and HSV-induced Fc receptors on the mononuclear cells will be characterized; c) the effects of binding of IgG to HSV-induced Fc receptors on the HSV-infected mononuclear cells and on the induction of retinochoroiditis will be evaluated. Finally, (d) the effect of HSV-specific antibody and of the antiviral agents on the HSVG-infected mononuclear cells will be tested. If the validity of this hypothesis can be proven, our investigation will have important medical implications: a) The pathogenic process for neonatal herpetic retinochoroiditis will be clarified, and an effective means of preventing and treating the disease will be found; b) the biological role of Fc receptors in the pathogenesis of herpetic retinochoroiditis will be identified; and c) the findings of this investigation will shed some light in our understanding of pathogenesis of retinochoroiditis in the newborn produced by other viruses, such as varicella-zoster, cytomegalo, measles and rubella viruses.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001578-12
Application #
3256032
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1976-09-30
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Overall Medical
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Zhang, Jiayi; Ackman, James B; Xu, Hong-Ping et al. (2011) Visual map development depends on the temporal pattern of binocular activity in mice. Nat Neurosci 15:298-307
Inoue, Y; Oh, J O; Minasi, P (1991) Protective effect of anti-glycoprotein D antibody on herpetic chorioretinitis in newborn rabbits. Curr Eye Res 10 Suppl:159-65
Rabinovitch, T; Oh, J O; Minasi, P (1990) In vivo reactivation of latent murine cytomegalovirus in the eye by immunosuppressive treatment. Invest Ophthalmol Vis Sci 31:657-63
Hatano, H; Oh, J O; Ou, K H et al. (1988) Induction of Fc and C3b receptors on rabbit corneal cells by herpes simplex virus. Invest Ophthalmol Vis Sci 29:1352-6
Hatano, H; Oh, J O (1987) Effect of neuraminidase on Fc and C3b receptors on rabbit corneal cells infected with herpes simplex virus. Curr Eye Res 6:53-7
Friedlaender, R P; Oh, J O; Minasi, P et al. (1987) Protective effect of passive immunization on herpetic retinitis of newborn rabbits. Curr Eye Res 6:161-6
Ohashi, Y; Oh, J O; Ou, K H et al. (1986) Role of virus-infected mononuclear leukocytes in herpetic chorioretinitis of newborn rabbits. Invest Ophthalmol Vis Sci 27:1459-65
Oh, J O (1986) Type 2 herpes simplex virus infections. Yonsei Med J 27:1-6
Oh, J O (1985) Immunology of viral infections. Int Ophthalmol Clin 25:107-16
Oh, J O; Minasi, P (1985) Role of lymphocyte and antibody in the pathogenesis of immune-mediated herpetic uveitis. Curr Eye Res 4:685-91

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