April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Characterization of Resident Corneal Leukocytes in Adenovirus Type 37 Infection
Author Affiliations & Notes
  • D. Zhu
    Harvard Medical School, Boston, Massachusetts
  • X. Zhou
    Ophthalmology, Massachusetts Eye and Ear Infirmary - Harvard Medical School, Boston, Massachusetts
  • J. Chodosh
    Ophthalmology, Massachusetts Eye and Ear Infirmary - Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  D. Zhu, None; X. Zhou, None; J. Chodosh, None.
  • Footnotes
    Support  NIH RO1 EY013124 and P30 EY014104, Research to Prevent Blindness, Falk Foundation, and Mass Lions Eye Research Fund
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3880. doi:
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      D. Zhu, X. Zhou, J. Chodosh; Characterization of Resident Corneal Leukocytes in Adenovirus Type 37 Infection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3880.

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Abstract

Purpose: : To characterize the changes in distribution, morphology, and maturation of resident antigen-presenting cells (APCs) of the corneal stroma in response to human adenovirus type 37 (HAdV-37) infection using a mouse model.

Methods: : HAdV-37 or Cy3-labeled HAdV-37 was injected into the corneal stroma of C57BL/6J mice using a gas-powered microinjection system and glass micropipette needle. Control corneas were untouched or injected with dialysis buffer control. Mice were sacrificed at 30 min, 4 hr, 16 hr, and 24 hr post infection. Corneas were immunostained for CD11b (myeloid cell), CD11c (dendritic cell), CD86 (costimulatory molecule), and F4/80 (macrophage), and whole-mounted for confocal microscopy. Flow cytometry was also performed using anti-CD86 and CD11c antibodies at 16 hr post infection.

Results: : Untouched corneas revealed a large population of round and spindle-shaped CD11b+ and CD11c+ cells in the anterior stroma; a smaller CD11b+ population was seen in the posterior stroma. The density of CD11b+ and CD11c+ cells decreased from the periphery towards the center. Star-shaped CD86+ cells were seen only in the periphery, suggesting the localization of immature myeloid cells (CD11b+CD86-) in the central cornea. At 30 min post infection, Cy3-HAdV-37 was noted in CD11b+/-, CD11c+/-, and CD86+/-, but not F4/80+ cells. As early as 4 hr post-infection, upregulation of CD86 was observed in the corneal periphery indicating the possible maturation of resident APCs. At 16 hr post infection, CD86+ cells were observed in the paracentral cornea. Notably, a large influx of small, multi-lobed, CD11b+CD11c-CD86- cells (neutrophils) were seen throughout the stroma of infected corneas at 16 hr post infection. The observation of CD86 upregulation and neutrophil infiltration was validated by flow cytometry.

Conclusions: : These data suggest that the maturation of resident corneal APCs may be a relatively early event in response to adenovirus infection in the cornea. Moreover, HAdV-37 appears capable of infecting all resident corneal cells except for F4/80+ macrophages.

Keywords: adenovirus • inflammation • cornea: stroma and keratocytes 
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