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A proteomic characterization of aqueous humor in patients with exfoliation glaucoma. The anterior chamber, or front compartment of the eye, is filled with a watery fluid called aqueous humor, which provides the cornea and the lens with oxygen and vital nutrients. The aqueous humor also provides the necessary intraocular pressure (IOP) to maintain the shape of the eye. It is secreted into the posterior chamber (the fluid compartment behind the iris) by the ciliary body, and is filtrated through the trabecular meshwork of the anterior chamber. Glaucoma is a progressive optic neuropathy (a disease of the optic nerve) characterized by a specific pattern of optic nerve head and visual field damage. It is the leading cause of blindness in the Western world, and the second leading cause worldwide. Damage to the visual system in glaucoma is due to the death of the retinal ganglion cells, the axons of which comprise the optic nerve and carry the visual impulses from the eye to the brain. Glaucoma represents a final common pathway resulting from a number of different conditions that can affect the eye, many of which are associated with elevated IOP. The exfoliation syndrome (EXS) is characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues. When averaged across the globe, it is the most common identifiable cause of glaucoma worldwide (exfolitation glaucoma - EXG), and is in particular frequent in the Scandinavian countries. Recently, proteomic analysis has provided new insights into the pathogenesis of glaucoma. Changes in the extracellular matrix and alterations in the cytoskeletal proteins of the trabecular meshwork have been identified. Proteomic study has also provided new evidence to propose the role of oxidative damage in the neurodegeneration in glaucoma. We want to utilize proteomic analyzes of aqueous humor from patients to elucidate new aspects of EXG. By comparing the protein changes in diseased and healthy aqueous, central target or candidate proteins can be identified. The elucidation of their functions may help to understand the disease process and aid future treatment. Aqueous humor will be collected as part of the operative procedure of cataract from 10 patients with EXS without glaucoma, 10 patients with EXG and 10 patients without EXS (controls). The samples will be analyzed primarily by two-dimensional gel electrophoresis, and if there will be time also twodimensional liquid chromatography, both in combination with mass spectrometry. References Shimizu A, Nakanishi T, Koyama R, Ikeda T. [Proteomics in clinical research: new approach of mass spectrometry]. Rinsho Byori 2002; 50: 169–172. Yamane K, Minamoto A, Yamashita H, Takamura H, Miyamoto-Myoken Y, Yoshizato K, Nabetani T, Tsugita A, Mishima HK. Proteome analysis of human vitreous proteins. Mol Cell Proteomics 2003; 2: 1177–1187. Wu CW, Sauter JL, Johnson PK, Chen CD, Olsen TW. Identification and localization of major soluble vitreous proteins in human ocular tissue. Am J Ophthalmol 2004; 137: 655– 661. 104. Gao BB, Clermont A, Rook S, Fonda SJ, Srinivasan VJ, Wojtkowski M, Fujimoto JG, Avery RL, Arrigg PG, Bursell SE, Aiello LP, Feener EP. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med 2007; 13: 181–188. Neal RE, Bettelheim FA, Lin C, Winn KC, Garland DL, Zigler JS Jr. Alterations in human vitreous humour following cataract extraction. Exp Eye Res 2005; 80: 337–347. L. Paulson, PS. Eriksson, M. Curtis. Progenitor cells in the brain in normal and diseased brain: an immature cell population defined by their location and unique pattern of protein expression. Journal of Current Biotechnology. Curr Pharm Biotechnol. 2007 Jun;8(3):117-25. Linda Paulson, Rita Persson, Gösta Karlsson, Rolf Ekman Jurek Silberring and Ann Brinkmalm. The capacity and limitations of MS in neuroscience. J Mass Spectrom. 2005 Feb;40(2):20213.. This project will be performed at Rikshospitalet, Oslo and at the University of Oslo. Contact: [email protected] or [email protected]