May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Spontaneous Bacterial Keratitis in CD36 Knockout Mice
Author Affiliations & Notes
  • M. S. Gregory
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • R. N. Barcia
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • S. Heimer
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • C. Hackett
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • M. S. Gilmore
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • B. R. Ksander
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  M.S. Gregory, None; R.N. Barcia, None; S. Heimer, None; C. Hackett, None; M.S. Gilmore, None; B.R. Ksander, None.
  • Footnotes
    Support  NIH Grant EY016486
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2824. doi:https://doi.org/
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      M. S. Gregory, R. N. Barcia, S. Heimer, C. Hackett, M. S. Gilmore, B. R. Ksander; Spontaneous Bacterial Keratitis in CD36 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2824. doi: https://doi.org/.

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

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Abstract

Purpose: : The corneal epithelium expresses CD36, a class B scavenger receptor with many ligands, including: TSP-1, oxidized LDLs, oxidized phospholidpids, and apoptotic cells. In addition to these scavenging functions, CD36 has been implicated in the innate immune response to Staphylococcus aureus and functions as a co-receptor that facilitates TLR2/6 signaling. Although Staphylococcus are found in the normal flora of the ocular surface, mice are protected from infection and do not develop spontaneous bacterial keratitis. We hypothesize that in the absence of CD36, mice will not be protected from the normal ocular surface flora and will develop spontaneous bacterial keratitis.

Methods: : Corneas of CD36 KO and wild-type C57BL/6 mice were screened via slit lamp. Corneas were classified as either: (i) normal, (ii) mild defect, or (iii) severe defect. Corneas were sectioned, stained, and examined microscopically. Bacterial load and species in corneal tissue was determined by: (i) gram stain and ChromAgar, (ii) PCR and sequencing. S. aureus conjugated to FITC was used to study bacterial binding.

Results: : With age, CD36 KO mice develop mild corneal defects characterized by (i) a thickened epithelial basement membrane, (ii) increased laminin deposition, and (iii) a mild infiltrate of F4/80+ macrophages in the underlying stroma. The corneal defects observed in CD36 KO mice increased in frequency and severity with age, and the increased severity of the defects was accompanied by increased colonization of Staphylococcus zylosus. Bacterial quantification revealed high levels ofS. zylosus in corneas with severe defects, bur not in the wild-type controls. In addition, severe corneal defects showed a massive CD45+ infiltrate (mainly neutrophils) in the anterior part of the cornea. When incubated with FITIC conjugated S. aureus, corneas from wild-type C57BL/6 mice or normal CD36 KO mice showed low levels bacterial binding. In contrast, CD36 KO corneas with mild defects showed significantly increased S. aureus binding in the location of the defect.

Conclusions: : CD36 KO mice develop spontaneous bacterial keratitis. We postulate that the lack of CD36 leads to deposition of extracellular matrix near the basement membrane, which, with time, disrupts the outer layers of the corneal epithelium, allowing for increased binding of commensal bacteria. Since CD36 KO mice also have defective TLR-2 signaling, mice are not protected and develop spontaneous keratitis. This is the first report of spontaneous bacterial keratitis in mice.

Keywords: keratitis • Staphylococcus • immunomodulation/immunoregulation 
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