Investigation of the peptidoglycan sensing molecule, PGLYRP-2, in murine inflammatory uveitis

Jenna S. Clowers, Jordan J. Allensworth, Ellen Lee, Holly Rosenzweig

Research output: Contribution to journalArticle

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Abstract

Background/Aim: Peptidoglycan (PGN) recognition proteins (PGLYRPs) are innate immune molecules that recognise bacterial cell wall PGN, and participate in several inflammatory diseases such as arthritis. We sought to elucidate the contribution of PGLYRPs in murine uveitis (intraocular inflammatory disease) elicited by PGN, and the extent to which systemically administered PGN alters uveitis compared with arthritis versus locally triggered ocular responses. Methods: Mice deficient for PGLYRP-2, PGLYRP-3 or PGLYRP-4 were administered PGN by an intraperitoneal or intraocular injection. Arthritis was assessed by near-infrared imaging and histopathology, while uveitis was measured by intravital videomicroscopy and histopathology. Results: Systemic PGN exposure predisposed to arthritis through a PGLYRP-2 dependent mechanism. By contrast, systemic PGN exposure did not predispose to uveitis, and PGLYRP-2 deficiency had no impact on the development the uveitis. When PGN was administered locally, a robust uveitis ensued, which occurred independently of PGLYRP-2. Regardless of whether PGN was administered systemically or locally, neither PGLYRP-3 nor PGLYRP-4 deficiency significantly altered ocular inflammation compared with wild-type control animals. Conclusions: Our findings highlight the complexity of PGLYRPs and how PGLYRP-2 may use different molecular pathways in the joints versus eyes. Collectively, our results support a non-essential or redundant role for PGLYRPs-2, -3, -4 in uveitis.

Original languageEnglish (US)
Pages (from-to)504-510
Number of pages7
JournalBritish Journal of Ophthalmology
Volume97
Issue number4
DOIs
StatePublished - Apr 2013

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Peptidoglycan
Uveitis
Arthritis
Protein Deficiency
peptidoglycan recognition protein
Intraocular Injections
Video Microscopy
Wild Animals
Intraperitoneal Injections
Cell Wall
Joints

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Investigation of the peptidoglycan sensing molecule, PGLYRP-2, in murine inflammatory uveitis. / Clowers, Jenna S.; Allensworth, Jordan J.; Lee, Ellen; Rosenzweig, Holly.

In: British Journal of Ophthalmology, Vol. 97, No. 4, 04.2013, p. 504-510.

Research output: Contribution to journalArticle

Clowers, Jenna S. ; Allensworth, Jordan J. ; Lee, Ellen ; Rosenzweig, Holly. / Investigation of the peptidoglycan sensing molecule, PGLYRP-2, in murine inflammatory uveitis. In: British Journal of Ophthalmology. 2013 ; Vol. 97, No. 4. pp. 504-510.
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