Investigators and Projects
Ocular inflammation (uveitis) presents with an incidence of approximately 0.2% of the population in the UK. Uveitis is a chronic disease and 40% of sufferers go on to develop severe visual impairment. One of the leading causes of uveitis is autoimmune disease, where the immune response is directed against proteins that are expressed specifically in the eye.
Interphotoreceptor retinoid binding protein (IRBP), which is now known as retinol binding protein-3 (RBP-3), is often a target of autoimmune attack. RBP-3 is a high molecular weight glycolipoprotein found in the interphotoreceptor matrix , a space between the photoreceptors and the retinal pigment epithelium. The principle function of RBP-3 is to traffic retinoids (Vitamin A) from the RPE to the photoreceptors in the visual cycle. It also helps to regenerate rhodopsin in bleached rod outer segments. In addition, this protein may play a role in retinal development as RBP-3 is upregulated during early retinal differentiation. RBP-3 is made up of four subunits, each of which is a functional unit i.e. able to bind one molecule of retinol. Each of these subunits share 30-40% sequence homology and the whole molecule is 1234 amino acids in length.
Current research uses peptides found in the first subunit of the protein to study the immune response to RBP-3 in specific murine models. In our lab the production of recombinant murine RBP-3 subunits of the whole protein has allowed the study of the immune response to RBP-3, including the identification of possible pathogenic peptides that have not yet been uncovered. New pathogenic peptides would also allow the study of phenomena such as epitope spreading, which to date have been difficult to analyse.
Kerr, E. C., Raveney, B. J. E., Copland, D. A., Dick, A. D., and Nicholson, L.
B. (2008). Analysis of Retinal Cellular Infiltrate in Experimental Autoimmune
Uveoretinitis Reveals Multiple Regulatory Cell Populations.
J. Autoimmunity 31, 354-361
DOI:dx.doi.org/10.1016/j.jaut.2008.08.006
Kerr, E. C., Copland, D. A., Dick, A. D., and Nicholson, L. B. (2008). The
dynamics of leukocyte infiltration in experimental autoimmune uveoretinitis.
Progress in Retinal and Eye Research 27, 527-535
dx.doi.org/10.1016/j.preteyeres.2008.07.001.
Guyver, C.J., Copland, D.A., Calder, C.J., Sette, A., Sidney, J., Dick, A.D., and Nicholson, L.B. (2006) Mapping immune responses to mRBP-3 1-16 peptide with altered peptide ligands. Invest. Ophthalmol. & Vis. Sci. 47, 2027-2035.