Impaired Fas-Fas Ligand Interactions Result in Greater Recurrent Herpetic Stromal Keratitis in Mice.

Xiao-Tang Yin,Chelsea R Del Rosso,Jessicah Hard,Thomas A Ferguson,Chloe A Potter,Tammie L Keadle,John Herndon,Patrick M Stuart

doi:10.1155/2015/435140

Abstract

Herpes simplex virus-1 (HSV-1) infection of the cornea leads to a potentially blinding condition termed herpetic stromal keratitis (HSK). Clinical studies have indicated that disease is primarily associated with recurrent HSK following reactivation of a latent viral infection of the trigeminal ganglia. One of the key factors that limit inflammation of the cornea is the expression of Fas ligand (FasL). We demonstrate that infection of the cornea with HSV-1 results in increased functional expression of FasL and that mice expressing mutations in Fas (lpr) and FasL (gld) display increased recurrent HSK following reactivation compared to wild-type mice. Furthermore, both gld and lpr mice took longer to clear their corneas of infectious virus and the reactivation rate for these strains was significantly greater than that seen with wild-type mice. Collectively, these findings indicate that the interaction of Fas with FasL in the cornea restricts the development of recurrent HSK.

Highlights

Herpetic stromal keratitis (HSK) is a potentially blinding corneal inflammation that accompanies herpes simplex virus (HSV) infection of the eye
In order to address the role of Fas-Fas ligand (FasL) interactions during recurrent HSK, we have evaluated this interaction in a mouse Journal of Immunology Research model of induced recurrent HSK
It is clear that one way that the cornea attempts to limit inflammation following Herpes simplex virus-1 (HSV-1) infection is by increasing FasL expression which will more efficiently control the entrance of Fasexpressing inflammatory cells

Summary

Introduction

Herpetic stromal keratitis (HSK) is a potentially blinding corneal inflammation that accompanies herpes simplex virus (HSV) infection of the eye. In the face of this potentially blinding inflammatory attack, the cornea has the ability to reduce inflammation This includes the presence of immunosuppressive factors such as TGF-β [5], lack of vascularization [6, 7], and the presence of Fas ligand (FasL) [8,9,10,11,12,13,14]. FasL expressed in the retina and the cornea controls new vessel growth beneath the retina and in the cornea by inducing apoptosis of Fas-expressing vascular endothelial cells [15,16,17]. These studies clearly indicate that the presence of FasL in ocular tissues restricts inflammatory responses

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Conclusion