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RR Buggage, D Shen, N Tuaillon, GA Levy-Clarke, JA Smith, C-C Chan; Molecular Signatures of Infectious Agents in Ocular Neoplasms . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2591.
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Purpose: Infectious agents are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which infectious pathogens have been implicated in the disease pathogenesis. Using molecular analysis we sought to investigate the role of infectious agents in ocular neoplasms. Methods: Ocular tumors from patients known to have or suspected to have a systemic infectious disease were examined with routine histology and immunohistochemistry and diagnosed using standard histopathologic critieria. Microdissection [either by laser capture (Arcturus) or manually] was performed to remove neoplastic cells from the ocular lesions. PCR for specific infectious agents was performed on the microdissected neoplastic cells and the results were confirmed by Southern blot hybridization. The gene-specific PCR primers were as follows: 5'-GGA ACT GCA TCC GTT CAT GAG-3' sense and 5'-TCT TTA AAG CGT TCG TGG TC-3' antisense for T. gondii B1 gene; 5'-TCC GTG TTG TCT ACG TCC AG-3' sense and 5'-AGC CGA AAG GAT TCC ACC AT-3' antisense for HHV-8; 5'-GAC GAG GGG CCA GGT ACA-3' sense and 5'-GCA GCC AAT GCT TCT TGG ACG T-3' antisense for EBV; 5'-CCA TCAC CAG CAG CTA GAT AGC-3' sense and 5'-AGT TGC TGG TAT TCT CGC CTT AAT-3' antisense for the HTLV-1 gag gene and 5'-AAT TCA TTC AAA CAT CTG AC-3' sense and 5'-GGC AGT TGT TTT AAG AAA AG-3' antisense for the HTLV-1 pol gene. Results: Ocular tumors including a conjunctival papilloma, conjunctival lymphoma, and primary intraocular lymphomas of both T and B-cell phenotype were diagnosed. By conventional pathology no evidence of a microorganism was identified in any of the ocular tumors. Using microdissection and PCR we detected HPV type 33 DNA in the conjunctival papilloma. In two conjunctival lymphomas and one case of intraocular lymphoma from HTLV-1 infected patients we identified the presence of HTLV-1 gene sequences in the neoplastic cells. In the studied cases of B-cell primary intraocular lymphoma we found DNA for HHV-8 (6/32), EBV (2/21), and Toxoplasma gondii (2/16). Conclusion: Our findings confirm the oncogenic potential of infectious agents in the eye and raise the possibility that both benign and malignant ocular neoplasms can possibly be prevented or treated with antibiotic therapy.
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