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M.D. Trousdale, Z. Zhu, D. Stevenson, J.E. Schechter, T. Ritter, A.K. Mircheff; Expression of Soluble TNF Inhibitor Gene in the Lacrimal Gland Promotes Recovery of Tear Production, Tear Stability and Reduced Immunopathology in Rabbits with Autoimmune Dacryoadenitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2516.
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Purpose: Evaluate the effect of adenovirus-mediated transfer of soluble TNF-inhibitor gene and expression of the transgene protein in rabbit lacrimal gland with induced autoimmune dacryoadenitis. Methods: Autoimmune dacryoadenitis was induced in adult female NZW rabbits by injecting peripheral blood lymphocytes (PBL), previously activated by 5 days of co-culture with autologous lacrimal acinar cells in a mixed cell reaction. Two weeks later, after tear production and tear stability started to decline, an adenoviral vector carrying the TNF-inhibitor gene (AdTNFRp55-Ig) was injected (1 X 108 pfu/gland) directly into the lacrimal gland. Tear production was monitored by Schirmer test and tears were collected for detection of TNF-inhibitor protein. Cornea surface was evaluated by determining tear breakup time and rose bengal staining. Frozen lacrimal gland sections were stained for CD4, CD8, rabbit thymic lymphocyte antigen (RTLA) and CD18 antigen expression. Results: The average Schirmer score for rabbits with autoimmune disease started at 7.6 was 4.5 after 2 weeks and 3.9 at week 4. Following gene therapy at 2 weeks, tear production returned to normal levels of 8.1 by week 4. Tear BUT dropped from 20 to 11.3 seconds between 0 and 2 weeks in the untreated group. In the treated group, tear BUT improved to 16 seconds while untreated scores continued to decline. Rose bengal scores started at 0.2 and increased to 2.6 following induction of disease. Gene therapy resulted in a reduced staining (1.6) whereas rose bengal scores in untreated animal continued to increase to 3.4. In the lacrimal gland, the CD4 to CD8 ratio in the disease group was 4:1 compared to 1:2 in the treated group. RTLA and CD18+ cells were reduced approximately 50% following gene therapy. Conclusions: Gene therapy treatment of rabbits with induced autoimmune dacryoadenitis resulted in improved basal tear production, increased tear stability and reduced rose bengal staining of the cornea.
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