April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Adeno-Associated Virus Vector Mediated vIL-10 Gene Therapy for Autoimmune Dacryoadenitis in a Rabbit Model
P. B. Thomas; D. M. Samant; Y. Wang; S. Selvam; D. Stevenson; A. K. Mircheff; J. E. Schechter; F. Apparailly; M. D. Trousdale
Author Affiliations & Notes
  • P. B. Thomas
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
  • D. M. Samant
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
  • Y. Wang
    Physiology and Biophysics,
    University of Southern California, Los Angeles, California
  • S. Selvam
    Mork Family Dept. of Chemical Engineering,
    University of Southern California, Los Angeles, California
  • D. Stevenson
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
  • A. K. Mircheff
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
    Physiology and Biophysics,
    University of Southern California, Los Angeles, California
  • J. E. Schechter
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
    Cell and Neurobiology,
    University of Southern California, Los Angeles, California
  • F. Apparailly
    Hospital St Eloi, Montpellier, France
  • M. D. Trousdale
    Ocular Surface Center, Doheny Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships  P.B. Thomas, None; D.M. Samant, None; Y. Wang, None; S. Selvam, None; D. Stevenson, None; A.K. Mircheff, None; J.E. Schechter, None; F. Apparailly, None; M.D. Trousdale, None.
  • Footnotes
    Support  EY12689, EY05801, EY10550, EY03040 and grants from RPB and Allergan Pharmaceutical Company.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3654. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Adeno-Associated Virus Vector Mediated vIL-10 Gene Therapy for Autoimmune Dacryoadenitis in a Rabbit Model
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      P. B. Thomas, D. M. Samant, Y. Wang, S. Selvam, D. Stevenson, A. K. Mircheff, J. E. Schechter, F. Apparailly, M. D. Trousdale; Adeno-Associated Virus Vector Mediated vIL-10 Gene Therapy for Autoimmune Dacryoadenitis in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3654.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : To evaluate the effect of adeno-associated virus (AAV) vector mediated vIL-10 gene expression on lacrimal gland immunopathology and ocular surface disease in a rabbit model of induced autoimmune dacryoadenitis (ID).

Methods: : An inferior LG was excised from each rabbit, epithelial cells were purified and cultured for 2 days, gamma irradiated, and then co-cultured for 5 days with autologous peripheral blood lymphocytes. Autoimmune dacryoadenitis was induced in rabbits by autoadoptive transfer of activated PBL from the autologous mixed cell reaction. Schirmer test, tear break up time (BUT) and rose Bengal staining were done to assess clinical disease. After confirming disease at 4 weeks an AAV vector carrying the vIL-10 gene was injected into the remaining inferior LG of the treatment group (ID/Rx). All LG were removed for analysis at 16 weeks post disease induction. Cryosections were immunostained to quantify the CD4, CD8, RTLA (Rabbit T Lymphocyte Antigen), MHC II and CD18 expression. One portion of the gland was used for cytokine analysis by real time RT-PCR.

Results: : The tear production was decreased in the ID group and partially restored within two weeks of Rx. Tear BUT and rose Bengal score also showed overall improvement by the end of the study. Histopathological examination of ID group’s LG revealed some large scattered lymphocytic foci and areas of altered or distorted acini. In the ID/Rx group the lacrimal glands had scattered small lymphocytic foci around ducts and venules. The CD4:CD8 ratio was approximately 1:1 in normal animals, 8:1 in ID animals, and 0.4:1 in the ID/Rx group. CD18 expression was almost 5 fold less in the ID/Rx group. There was no significant difference between TNF-alpha and IFN-gamma mRNA transcripts in the ID and ID/Rx group. However, IL-10, IL-4 and IL-6 transcripts increased in ID/Rx group compared to ID group.

Conclusions: : Animals with experimentally induced autoimmune dacryoadenitis appear to benefit from AAV mediated vIL-10 gene therapy. Tear production increased, rose Bengal staining decreased and lacrimal gland histopathology decreased following gene therapy. The cytokine expression profile suggested that the response may have involved induction of CD8+ regulatory cells.

Keywords: lacrimal gland • cornea: tears/tear film/dry eye • autoimmune disease 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept