April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Spontaneous Autoimmune Inflammation of the Ocular Surface Mucosa in Aged CD4-DNTGFβRII Mice
Author Affiliations & Notes
  • Stephen C. Pflugfelder
    Ophthal-Ocular Surf Ctr,
    Baylor College of Medicine, Houston, Texas
  • Michael E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • Jerry Y. Niederkorn
    Ophthalmology, Univ Texas Southwestern Med Ctr, Dallas, Texas
  • John D. Pitcher, III
    Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California
  • Eugene Volpe
    Ophthalmology,
    Baylor College of Medicine, Houston, Texas
  • Niral Gandhi
    Ophthalmology,
    Baylor College of Medicine, Houston, Texas
  • William J. Farley
    Ophthalmology,
    Baylor College of Medicine, Houston, Texas
  • De-Quan Li
    Ophthalmology,
    Baylor College of Medicine, Houston, Texas
  • Cintia S. De Paiva
    Ophthalmology,
    Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  Stephen C. Pflugfelder, Allergan, Inc (C), Allergan, Inc. (F, R); Michael E. Stern, Allergan, Inc (E); Jerry Y. Niederkorn, Allergan, Inc. (F); John D. Pitcher, III, None; Eugene Volpe, None; Niral Gandhi, None; William J. Farley, None; De-Quan Li, None; Cintia S. De Paiva, Allergan, Inc. (F)
  • Footnotes
    Support  NIH Grant EY11915 (SCP) and EY018888 (CSDP), Allergan, Inc., Research to Prevent Blindness, Oshman Foundation, William Stamps Farish Fund and The Hamill Foundation
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2095. doi:
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      Stephen C. Pflugfelder, Michael E. Stern, Jerry Y. Niederkorn, John D. Pitcher, III, Eugene Volpe, Niral Gandhi, William J. Farley, De-Quan Li, Cintia S. De Paiva; Spontaneous Autoimmune Inflammation of the Ocular Surface Mucosa in Aged CD4-DNTGFβRII Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2095.

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Abstract

Purpose: : To investigate if defective TGF-β signaling in CD4+ T cells promotes development of autoimmune inflammation in ocular surface tissues.

Methods: : The ocular surface of 8- and 14-week old mice transgenic for directed expression of a dominant-negative form of TGF-receptor II (dnTGFRII), under the influence of the CD4 promoter (CD4-DNTGFβRII) was evaluated and compared to wild-type littermates of the same age. Corneal smoothness was assessed by reflection of a ring light. Corneal barrier function was assessed using fluorescent Oregon-Green Dextran (OGD). Conjunctival goblet cell density was counted in PAS stained sections. Immunohistochemistry evaluated CD4 and CD8 T cell infiltration of the cornea, conjunctiva and lacrimal gland. T helper (Th)-1, 2 and 17 associated cytokines were evaluated in cornea and conjunctiva by real time PCR.

Results: : 14 week-old CD4-DNTGFβRII exhibited a spontaneous dry eye phenotype compared to littermates: they had greater OGD staining and cornea surface irregularity, lower conjunctival goblet cell density and higher CD4+T cell infiltration in cornea, conjunctiva and lacrimal gland than 8 week-old mice. At 14 weeks of age, DNTGFBRII mice showed higher levels of MMP-9, IL-6, IL-17A and IFN-γ mRNA transcripts in both cornea and conjunctiva compared to wild-type control mice.

Conclusions: : Disruption of TGF-β signaling in CD4 T cells promotes spontaneous autoimmunity in cornea, conjunctiva and lacrimal gland that has features of dry eye disease. T cell infiltration of the cornea is rarely observed in other autoimmune mouse models of dry eye, suggesting that that functional TGF-β signaling prevents CD4+ T infiltration in the cornea.

Keywords: cornea: tears/tear film/dry eye • inflammation • conjunctiva 
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