June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Intravenously Injected Autologous, Ex Vivo-Activated Lymphocytes Adoptively Transfer Dry Eye Disease to Rabbits
Author Affiliations & Notes
  • Austin K Mircheff
    Dept of Physiology & Biophysics, Univ of Southern California, Los Angeles, California, United States
  • Yanru Wang
    Dept of Physiology & Biophysics, Univ of Southern California, Los Angeles, California, United States
  • Houman Hemmati
    Capricor Therapeutics, Inc, Beverly Hills, California, United States
  • Luis Rodriguez-Borlado
    Capricor Therapeutics, Inc, Beverly Hills, California, United States
  • Footnotes
    Commercial Relationships   Austin Mircheff, None; Yanru Wang, None; Houman Hemmati, Capricor Therapeutics, Inc (E); Luis Rodriguez-Borlado, Capricor Therapeutics, Inc. (E)
  • Footnotes
    Support  Capricor Therapeutics, Inc
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 462. doi:
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    • Get Citation

      Austin K Mircheff, Yanru Wang, Houman Hemmati, Luis Rodriguez-Borlado; Intravenously Injected Autologous, Ex Vivo-Activated Lymphocytes Adoptively Transfer Dry Eye Disease to Rabbits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):462.

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

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Abstract

Purpose : Dry eye disease is a manifestation of chronic, immune mediated inflammatory processes in the ocular surface tissues and lacrimal glands (LG). Biologically appropriate animal models are needed. Of theoretical and practical importance, immunocompetent rabbits are susceptible to adoptively-transferred DED, while immunocompetent rodents are not. Accordingly, we have designed a new, efficient protocol for adoptively transferring immune-mediated ocular surface inflammation to rabbits.

Methods : Microparticles (MP), which include exosomes that LG acinar cell secrete constitutively, are naturally microencapsulated samples of autoantigens from both the cytosol and the cells’ membrane-bounded compartments. MP were isolated from supernatant primary culture medium and used to prime dendritic cells (mDC) that had been matured from bone marrow monocytes and stimulated with LPS. Peripheral blood lymphocytes (PBL) were isolated from study animals (n=6); activated in ex vivo mixed cell reactions with MP-primed mDC; then reintroduced autologously via marginal ear veins. Ocular surface status was evaluated by rose Bengal (RB) staining and Schirmer I tear tests (STT-I) at baseline and then biweekly for 12 wk after PBL injection.

Results : One eye with high baseline RB score (1.5) and low STT-I score (6.0 mm/min) was excluded as spontaneously diseased. Ocular surface inflammation developed over bi-phasic time-courses in the remaining 11 eyes. RB scores increased to 0.8 ± 0.1 above baseline value of 0.8 ± 0.1) at wk 2, subsided at wk 2, and recrudesced at wk 8, suggesting a biphasic phenomenon. By wk 12, RB scores remained elevated 1.0 ± 0.1 above baseline in 5 eyes and 0.5 ± 0.1 above baseline in 5 eyes, but returned to baseline in 1 eye. STT-I scores decreased 3.4 ± 0.4 mm below baseline value of 9.0 ± 0.5 in 8 eyes, remained unchanged in 2 eyes, and increased 1.0 mm above baseline in 1 eye. By wk 12, STT-I scores remained decreased 2.1 ± mm in 7 eyes, unchanged in 1 eye, and increased 2.0 mm above baseline in 1 eye. The scores remitted together in only 1 eye. Preliminary H&E demonstrated extensive fatty infiltratrion in 1 LG and both inter-acinar infiltrates and periductal infiltrates of varying sizes and frequences in the remaining LG.

Conclusions : This may be an appropriate model for pathophysiology and treatment of mild-to-moderate DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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