PURPOSE: CD36 is a Class B scavenger receptor that is constitutively expressed in the corneal epithelium and has been implicated in many homeostatic functions, including the homeostasis of the epidermal barrier. The aim of this study is to determine (1) whether CD36 is required for the maintenance of the corneal epithelial barrier to infection, and (2) whether CD36-deficient mice present with an increased susceptibility to bacterial keratitis. METHODS: The corneas of CD36(-/-), TSP1(-/-), TLR2(-/-), and C57BL/6 WT mice were screened via slit lamp microscopy or ex vivo analysis. The epithelial tight junctions and mucin layer were assessed via LC-biotin and Rose Bengal staining, respectively. Bacterial quantification was performed on corneal buttons and GFP-expressing Staphylococcus aureus was used to study bacterial binding. RESULTS: CD36(-/-) mice develop spontaneous corneal defects that increased in frequency and severity with age. The mild corneal defects were characterized by a disruption in epithelial tight junctions and the mucin layer, an infiltrate of macrophages, and increased bacterial binding. Bacterial quantification revealed high levels of Staphylococcus xylosus in the corneas of CD36(-/-) mice with severe defects, but not in wild-type controls. CONCLUSIONS: CD36(-/-) mice develop spontaneous bacterial keratitis independent of TLR2 and TSP1. The authors conclude that CD36 is a critical component of the corneal epithelial barrier, and in the absence of CD36 the barrier breaks down, allowing bacteria to bind to the corneal epithelium and resulting in spontaneous keratitis. This is the first report of spontaneous bacterial keratitis in mice.
PURPOSE:CD36 is a Class B scavenger receptor that is constitutively expressed in the corneal epithelium and has been implicated in many homeostatic functions, including the homeostasis of the epidermal barrier. The aim of this study is to determine (1) whether CD36 is required for the maintenance of the corneal epithelial barrier to infection, and (2) whether CD36-deficient mice present with an increased susceptibility to bacterial keratitis. METHODS: The corneas of CD36(-/-), TSP1(-/-), TLR2(-/-), and C57BL/6 WT mice were screened via slit lamp microscopy or ex vivo analysis. The epithelial tight junctions and mucin layer were assessed via LC-biotin and Rose Bengal staining, respectively. Bacterial quantification was performed on corneal buttons and GFP-expressing Staphylococcus aureus was used to study bacterial binding. RESULTS:CD36(-/-) mice develop spontaneous corneal defects that increased in frequency and severity with age. The mild corneal defects were characterized by a disruption in epithelial tight junctions and the mucin layer, an infiltrate of macrophages, and increased bacterial binding. Bacterial quantification revealed high levels of Staphylococcus xylosus in the corneas of CD36(-/-) mice with severe defects, but not in wild-type controls. CONCLUSIONS:CD36(-/-) mice develop spontaneous bacterial keratitis independent of TLR2 and TSP1. The authors conclude that CD36 is a critical component of the corneal epithelial barrier, and in the absence of CD36 the barrier breaks down, allowing bacteria to bind to the corneal epithelium and resulting in spontaneous keratitis. This is the first report of spontaneous bacterial keratitis in mice.
Authors: Kathryn J Moore; Joseph El Khoury; Lea A Medeiros; Kinya Terada; Changiz Geula; Andrew D Luster; Mason W Freeman Journal: J Biol Chem Date: 2002-09-17 Impact factor: 5.157
Authors: Lynda M Stuart; Susan A Bell; Cameron R Stewart; Jessica M Silver; James Richard; Julie L Goss; Anita A Tseng; Ailiang Zhang; Joseph B El Khoury; Kathryn J Moore Journal: J Biol Chem Date: 2007-07-09 Impact factor: 5.157
Authors: Srihari Narayanan; Rachel L Redfern; William L Miller; Kelly K Nichols; Alison M McDermott Journal: Ocul Surf Date: 2013-01-29 Impact factor: 5.033
Authors: Bruce R Ksander; Paraskevi E Kolovou; Brian J Wilson; Karim R Saab; Qin Guo; Jie Ma; Sean P McGuire; Meredith S Gregory; William J B Vincent; Victor L Perez; Fernando Cruz-Guilloty; Winston W Y Kao; Mindy K Call; Budd A Tucker; Qian Zhan; George F Murphy; Kira L Lathrop; Clemens Alt; Luke J Mortensen; Charles P Lin; James D Zieske; Markus H Frank; Natasha Y Frank Journal: Nature Date: 2014-07-02 Impact factor: 49.962