Dynamics of the Ocular Immune Response During Uveitis

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Abstract Uveitis is a potentially blinding disease’s that are a leading cause of blindness among Americans. Characteristic of autoimmune diseases is marked relapsing and remitting inflammation of the target tissue. In the case of autoimmune uveitis, the eye is the target and because the eye allows for the penetration of light through much of the organ, study of the immune response in the eye has a particular advantage. This advantage being that light could be used as a non-invasive method to label cells that are present during inflammation and migrate out as the inflammation resolves. Experimental autoimmune uveitis (EAU) is the most widely used model of autoimmune uveitis. We propose to generate and validate a novel mouse that stably expresses a light inducible expression system that can be used to label cells in the eye during any point before or during EAU (Specific Aim 1). Our hypothesis is that a transgenic mouse that expresses photoactivatable Cre will be an excellent tool to permanently label cells in the eye. Currently, the only long-term labeling systems available rely on the injection of compounds that can be toxic and diffuse out of the target tissue. This proposal utilizes a novel photoactivatable system that drives Cre activation to induce permanent genetic changes that allow for permanent labeling of the target cells. A second-generation system has been demonstrated in mammalian cell lines, and in mice by transfecting the target cells. In this proposal we will generate a novel mouse line that stably expresses the transgenes for the purpose of answering the immunological questions that relate to an organ that readily allows for light to pass through. Importantly, this will allow for many future studies that can be answered through a non-invasive labeling of cells at any time in any tissue that allows for the penetration of light.