Bruce Ksander

Molecular Solutions to Low Vision Resulting from Battlefield Injuries

This research project will determine the efficacy of using soluble Fas Ligand (sFasL) to prevent and/or treat sight-threatening corneal inflammation and scarring induced by trauma. It does not include any research on corneal transplants. The major goals of this grant are: (i) Determine the capacity of corneas treated with adenoviral vectors containing the cDNA for sFasL to suppress corneal inflammation and scarring following burns (chemical or thermal); (ii) Determine if sFasL treatment prevents the infiltration and/or activation of innate inflammatory cells within corneas following burns; (iii) Determine if sFasL treatment prevents the infiltration and/or activation of innate inflammatory cells within corneas following burns; (iv) Develop a purified recombinant sFasL protein that is easily delivered via “eye-drops” to the cornea. Determine the effectiveness of these eye-drops in preventing corneal inflammation and scarring following burns.

The Immunobiology of Corneal Transplants

The long-term goals of this project are to understand: (a) why primary orthotopic corneal allografts are so well tolerated (display immune privilege), and (b) why grafts in “high-risk” eyes fare so poorly. Two hypotheses are tested: Hypothesis 1. Atypical expression of alloantigens and expression of immunomodulatory molecules on corneal cells contribute to the cornea’s immune privileged status. Hypothesis 2. MHC class II and/or minor H alloantigen expression rob the corneal epithelium of its graft-acceptance promoting capacity. Our experiments will enable us to discover novel cellular and molecular mechanisms with which to create protocols with greater power to promote graft acceptance in clinical situations where graft failure is common.