Infectious pathogens including bacteria, mycobacteria, fungi, viruses and protozoa are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. Typically infectious ocular diseases are characterized by an inflammatory response to rid the host of the offending microorganism. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which routine clinical investigations reveal no direct evidence of a causative infectious pathogen. Our group is interested in investigating the role of infectious pathogens in the pathogenesis of ocular diseases that may lead to better diagnostic methods and treatment strategies. In a clinical study members of our group have described for the first time the presence of corneal lesions associated with elevated immunoglobulin levels and in Jamaican patients infected with the human T-cell lymphotropic virus (HTLV-1) which was already known to cause uveitis. Using microdissection and PCR on a conjunctival specimen removed from one of these patients we have identified for the first time HTLV-1 genes and rearrangements of the T-cell receptor gene in a patient with conjunctival adult T-cell leukemia/lymphoma. As result of these findings clinical studies have been planned to further define the spectrum of ocular disease associated with HTLV-1 in patients living in Jamaica and to determine the mechanism by which the viral infection causes the ocular complications. In other laboratory studies using a similar technique we have demonstrated the presence of a viral pathogen, HPV type 33, not previously known to cause human ocular disease in a benign conjunctival papilloma in a patient with AIDS. Additionally, we have found evidence of toxoplasma DNA sequences in the malignant lymphoid cells in a few immunocompetent patients with primary intraocular lymphoma. These findings are significant because they suggest the oncogenic potential of infectious agents in the eye and raise the possibility that both benign and malignant forms of neoplastic ocular diseases can possibly be prevented or treated by antibiotic therapy. Finally, working with an experimental murine model of human toxoplasmosis we showed that in the absence of apoptosis (programmed cell death) in mice experimentally infected with toxoplasma cysts, cytokines are protective against the infection. This data is exciting because it suggests cytokines may be used therapeutically to treat infectious ocular disease in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000373-01
Application #
6546723
Study Section
(LI)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56
de Smet, Marc D; Shen, De Fen; Pepose, Jay et al. (2003) Microdissection combined with the polymerase chain reaction to identify potentiating viral co-infection in patients with HIV/AIDS with ocular infection. Can J Ophthalmol 38:207-13
Shen, D F; Matteson, D M; Tuaillon, N et al. (2001) Involvement of apoptosis and interferon-gamma in murine toxoplasmosis. Invest Ophthalmol Vis Sci 42:2031-6
Shen, D F; Herbort, C P; Tuaillon, N et al. (2001) Detection of Toxoplasma gondii DNA in primary intraocular B-cell lymphoma. Mod Pathol 14:995-9
Buggage, R R; Levy-Clarke, G A; Smith, J A (2001) New corneal findings in human T-cell lymphotrophic virus type 1 infection. Am J Ophthalmol 131:309-13