We propose to study the effect of local ocular factors on the pathogenesis and control of herpes simplex virus (HSV) infections of the eye. In the experiments proposed here we will: (1) Test corneal specimens from patients with herpetic eye disease and from control cases to reveal latent virus infection of the cornea; (2) develop animal models of corneal latency; (3) examine the effect of topical (local) mediators, particularly adrenergic drugs, on recurrent viral shedding from the eye in experimental animal models; (4) evaluate the effect of these same mediators on HSV replication in corneal organ culture and cell culture systems. To prevalence and pathogenesis of latent HSV in cornea will be determined by co-cultivation and immunochemical staining of corneas removed from patients with herpetic eye disease at keratoplasty. We will also develop an in vitro model of HSV latency in animal corneas and compare reactivation in infected corneas and ganglia. We will also study the ocular shedding of virus in latently infected animals following locally applied adrenergic drugs and other mediators (e.g. prostaglandins, interferons) to test the hypothesis that local factors specifically affect the ability of the ocular tissues to support HSV replication. These compounds will be tested in latently infected animals, corneal organ cultures and cell culture systems. The goal of this research is to examine local treatment with specific mediators for their potential to prevent or enhance recurrent herpetic eye disease in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY003917-04A2
Application #
3258384
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-08-01
Project End
1991-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
LaVail, J H; Carter, S R; Topp, K S (1993) The retrograde tracer Fluoro-Gold interferes with the infectivity of herpes simplex virus. Brain Res 625:57-62
Margolis, T P; Dawson, C R; LaVail, J H (1992) Herpes simplex viral infection of the mouse trigeminal ganglion. Immunohistochemical analysis of cell populations. Invest Ophthalmol Vis Sci 33:259-67
Carter, S R; Pereira, L; Paz, P et al. (1992) A quantitative assay of retrograde transported HSV in the trigeminal ganglion. Invest Ophthalmol Vis Sci 33:1934-9
LaVail, J H; Meade, L B; Dawson, C R (1991) Ultrastructural immunocytochemical localization of herpes simplex virus (type 1) in trigeminal ganglion neurons. Curr Eye Res 10 Suppl:23-9
Margolis, T P; Ostler, H B (1990) Treatment of ocular disease in eczema herpeticum. Am J Ophthalmol 110:274-9
Margolis, T P; LaVail, J H; Setzer, P Y et al. (1989) Selective spread of herpes simplex virus in the central nervous system after ocular inoculation. J Virol 63:4756-61
Teitelbaum, C S; Streeten, B W; Dawson, C R (1987) Histopathology of herpes simplex virus keratouveitis. Curr Eye Res 6:189-94
Margolis, T; Togni, B; LaVail, J et al. (1987) Identifying HSV infected neurons after ocular inoculation. Curr Eye Res 6:119-26
Holland, G N; Togni, B I; Briones, O C et al. (1987) A microscopic study of herpes simplex virus retinopathy in mice. Invest Ophthalmol Vis Sci 28:1181-90
Zhang, W H; Briones, O; Dawson, C R (1986) Effect of autonomic mediators in recurrent shedding of herpes simplex in the rabbit eye. Curr Eye Res 5:79-84