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M. S. Gregory, J. Klocke, R. Barcia, S. Heimer, J. Zieske, M. S. Gilmore, B. R. Ksander; CD36 Is a Critical Component of the Corneal Epithelial Barrier to Infection. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3456.
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The healthy cornea has multiple barriers in place to prevent infection and is highly resistant to bacterial keratitis. However, when these barriers are breached the incidence of infection increases significantly. We previously demonstrated that CD36 KO mice develop spontaneous bacterial keratitis. CD36 is a Class B scavenger receptor with many functions including: uptake of apoptotic cells, co-receptor for TLR2/6 signaling, and inhibition of angiogenesis. We hypothesize that CD36 contributes to corneal resistance to infection because CD36 is critical in maintaining epithelial migration and adhesion. Corneas that lack CD36 develop epithelial defects with age resulting in a disruption of the epithelial barrier and spontaneous keratitis.
LC-biotin and Rose Bengal staining were used to examine the epithelial tight junctions and the mucin layer, respectively. Bacterial binding to the cornea was studied using FITC conjugated S. aureus. Corneal epithelial wounds were performed using a 1.5 mm trephine and blunt scalpel to remove the central epithelium without disrupting the basement membrane. Wound healing was monitored via slit lamp and microscopy. Corneal epithelial cells from CD36 KO and WT mice were immortalized with human papiloma virus E6/E7 genes.
CD36 KO mice develop corneal defects with age, characterized by: (i) disruption of epithelial tight junctions and the mucin layer, (ii) a thickened epithelial basement membrane and increased laminin deposition, (iii) F4/80+ macrophages infiltrating the stroma underlying the wound, and (iv) increased binding of FITC conjugated S. aureus. Following an epithelial wound, WT corneas completely re-epithelialized within 48 hrs and remained clear. By contrast, CD36 KO mice displayed delayed re-epithelialization and persistent inflammation. Histologically, wounds contained disorganized epithelium accompanied by neutrophil and macrophage infiltration in the underlying stroma. In addition, immortalized epithelial cells from CD36 KO mice were unable to migrate and adhere in culture as compared with WT epithelial cells.
CD36 is critical in maintaining the corneal epithelial barrier by contributing to proper epithelial cell: migration, adhesion, and formation of tight junctions. In the absence of CD36, the epithelial barrier and mucin layer are disrupted, allowing the normal corneal flora to bind.
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