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RW Crow, S Bose, D Stevenson, Z Zhu, AK Mircheff, JE Schechter, T Ritter, MD Trousdale; Apoptosis in Adenovirus-Mediated Transfer of TNF-Inhibitor Gene in a Rabbit Model of Induced Autoimmune Dacryoadenitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3136.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Gene transfer of anti-inflammatory cytokines might be an effective therapy for patients with Sjögren's syndrome, but it is not known if the transgene will have any deleterious effect on the lacrimal gland acinar cells. In this study, rabbit lacrimal glands with induced autoimmune dacryoadenitis and those with viral transduction were examined for presence of apoptosis. Methods: Experimental autoimmune dacryoadenitis was induced in rabbits by injecting the glands with peripheral blood lymphocytes that were pre-stimulated in an autologous mixed-cell reaction with purified acinar cells (AMCR-stimulated PBLs). In the treated group, adenovector carrying TNF-inhibitor gene (AdTNFRp55-Ig, 1x 108 pfu) was injected concurrently with AMCR-stimulated PBLs. TNF-inhibitor in the tear film was measured by ELISA, and apoptosis in histological sections of lacrimal gland was evaluated using the TUNEL technique. Dacryoadenitis-induced glands were examined at weekly intervals, with and without TNF-inhibitor transduction. Results: TNF inhibitor levels in the tears of transduced lacrimal glands peaked at 3 days and declined by day 7. Autoimmune dacryoadenitis lacrimal glands demonstrated a greater degree of apoptosis over normal controls. However, the treated glands showed little or no evidence of apoptosis at the end of 2 weeks. Conclusion: Experimentally induced autoimmune dacryoadenitis in rabbit lacrimal glands produces apoptosis of acinar cells, while in-vivo transduction with TNF-inhibitor gene appears to suppress the process. Gene therapy in autoimmune dacryoadenitis does not result in apoptotic cell death and may be useful as a therapeutic tool.
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