OCULAR HERPES SIMPLEX
Principal Investigator: Herbert Kaufman
Affiliation: Louisiana State University Health Sciences Center
Abstract: The specific aims of this competing renewal are to continue to seek antiviral drugs and drug delivery systems that will improve the treatment of ocular herpes infections, and to investigate possible underlying mechanisms that may make such treatments less effective. We will study thymidine kinase selective and DNA polymerase selective drugs, alone and in combination, to treat herpes infections of the stroma and herpes iritis without toxicity to the host, and test the anti-inflammatory and antiviral effects of cyclosporine, antiviral drugs, and lipoxygenase inhibitors and leukotriene receptor antagonists, alone and in combination, in conjunction with newly developed drug delivery systems to potentiate penetration into the eye. We will also test drug therapies that may prevent virus reactivation and recurrence of ocular herpetic disease, and investigate the molecular genetics of herpes reactivation. Using a primate model for clinical recurrences, we will determine whether a new drug [5'-ethynyl deoxyuridine (EnDU)] that specifically inhibits viral thymidine kinase and appears to have no effect on the host can prevent or modify recurrences. We will investigate, at the molecular level, the relationship between changes in the axonal transport mechanisms or signals conducted through the axonal transport mechanisms to the neuron cell body and changes in cell body gene expression that may lead to reactivation of latent HSV-1. We will examine the possibility that surgical trauma, possibly neuronal in nature, leads to reactivation of latent herpesvirus and subclinical herpetic disease after penetrating keratoplasty in man, as it does in rabbits. We will also continue to develop and test a new and rapid method of diagnosing recurrent superficial corneal herpesvirus infection which involves an immunologically specific reaction that can be completed in less than one hour. New and powerful methodologies will be employed, including high pressure liquid chromatography-mass spectrometry and various molecular biological techniques, such as northern blotting and antisense mRNAs. The ultimate goal of these studies is to improve our understanding of ocular herpevirus infection and thereby develop and test more specific treatments to cure this devastating and blinding eye disease.
Funding Period: 1978-02-01 - 1995-02-28
more information: NIH RePORT
- HSV-1 DNA in tears and saliva of normal adultsHerbert E Kaufman
Department of Ophthalmology, LSU Eye Center, New Orleans, LA 70112, USA
Invest Ophthalmol Vis Sci 46:241-7. 2005..To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals...
- Ocular herpes simplex virus type 1: is the cornea a reservoir for viral latency or a fast pit stop?David P Kennedy
Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2234, USA
Cornea 30:251-9. 2011..To present a review supporting and refuting evidence from mouse, rabbit, nonhuman primate, and human studies of herpes simplex virus type 1 (HSV-1) concerning corneal latency...
- Heat-induced reactivation of HSV-1 in latent mice: upregulation in the TG of CD83 and other immune response genes and their LAT-ICP0 locusChristian Clement
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
Invest Ophthalmol Vis Sci 50:2855-61. 2009..To determine changes in host gene expression in HSV-1 latent trigeminal ganglia (TG) after hyperthermic stress...
- Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivationBryan M Gebhardt
Lions Eye Research Laboratories, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2234, USA
J Ocul Pharmacol Ther 21:114-20. 2005..It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis...
- Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infectionHerbert E Kaufman
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center in New Orleans, New Orleans, LA, USA
J Ocul Pharmacol Ther 24:34-42. 2008..The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits...
- Effective treatment of ocular HSK with a human apolipoprotein E mimetic peptide in a mouse eye modelPartha S Bhattacharjee
Departments of Ophthalmology, School of Public Health, LouisianaState University Health Sciences Center, New Orleans, Louisiana 70112, USA
Invest Ophthalmol Vis Sci 49:4263-8. 2008....
- The high prevalence of herpes simplex virus type 1 DNA in human trigeminal ganglia is not a function of age or genderJames M Hill
Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
J Virol 82:8230-4. 2008..This is the first study that provides statistical analysis that documents that the prevalence of HSV-1 DNA in the human TG is not a function of either gender or age...
- Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1Partha S Bhattacharjee
Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Exp Eye Res 87:122-30. 2008..This is the first report linking a human gene, apoE4, as a risk factor for ocular herpes pathogenesis in a transgenic mouse model...
- Ocular HSV-1 latency, reactivation and recurrent diseaseHassanain S Toma
Louisiana State University Health Sciences Center, New Orleans, LA 70112 2234, USA
Semin Ophthalmol 23:249-73. 2008..This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data...