The purpose of this study was to investigate the expression of ECM proteins fibronectin and osteopontin in a spontaneous animal model for autoimmune uveitis to gain further information about these proteins and the role of ECM in a retinal disorder. A comprehensive understanding of autoimmune uveitis pathogenesis remains as yet elusive. Analysis of differentially expressed proteins in target tissues of healthy and diseased condition provides a basis for analysis of pathogenesis-associated processes. To this end, Bortezomib Proteasome inhibitor proteomic studies and subsequent evaluation have revealed several enlisted proteins, biomarkers and pathways in autoimmune uveitis contributing to a better understanding of disease development and progression. In a specific comparative proteomic analysis of retinal membrane protein enriched fractions, fibronectin, a protein of the ECM, was found to be upregulated in ERU. In order to evaluate this finding and further characterize its role in uveitis pathogenesis, we investigated the expression of fibronectin in vitreous and retina of control and uveitic samples since the vitreous body and the retina have been shown to play a crucial role in the pathogenesis of autoimmune uveitis. In the present study we demonstrated a significant downregulation of fibronectin in vitreous samples of ERU diseased horses compared to controls by western blotting experiments. Furthermore, we showed a positive immunoreactivity for fibronectin exclusively at the ILM of healthy equine retinas. This expression varied in uveitic retinas displaying a disintegrated pattern along the ILM expanding towards the vitreous. With these results we could again confirm that comparative proteomic analysis is a reliable tool to reveal expression changes of molecules and can provide a basis to suggest pathways potentially involved in disease pathogenesis when validated and further investigated. Fibronectin is a ligand to various intergrin receptors and thus mediates adhesion and interaction of cells with the ECM. The expression of fibronectin within the retina was investigated in several studies and inconsistent results were presented. While some immunohistochemical studies on retinal tissue of human eyes failed to detect fibronectin, studies in rat and human retinas demonstrated positive fibronectin immunoreactivity at the ILM. The ILM is the vitreo-retinal border that represents the connection between the retina and the vitreous body and was shown to be built by retinal Muiller cells that abut this basement membrane with their endfeet. In the present study immunohistochemical stainings of cultured equine Muiller cells and eqMC-7 cells confirmed the ability of Muiller cells to express fibronectin. It was reported that fibronectin is implicated in adhesion of cultured rat Muiller cells. Therefore, our results indicate that fibronectin might be produced by Muiller cells to anchor their endfeet membranes to the ILM and thus contribute to the attachment of the retina to the vitreous body.