Autoimmunity in uveitis and other chorioretinal diseases

Uveitis is an inflammation of the vascular layer of the eye, which includes the iris, ciliary body and choroid. However, in practice the term uveitis is usually used as a collective term for any form of intraocular inflammation. Uveitis is a major cause of visual impairment or even blindness. The pathogenesis of uveitis is not fully clarified, but a crucial role of autoimmune reactions has been suggested. Although humoral autoimmune reactions directed against retinal tissue are thought to play an important role in either initiation or modification of diverse chorioretinal disorders including uveitis, they were not as yet systematically measured and their possible clinical impact in retinal diseases was not examined. Understanding of autoimmune processes in ocular diseases might help to further elucidate their pathogeneses and may have consequences for the design of new diagnostic and treatment modalities. In order to improve the understanding of autoimmune processes in ocular diseases this thesis aims to assess the presence of humoral autoimmunity in uveitis and other chorioretinal diseases, including autoimmune retinopathy, and to gain insight in its role

Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient

Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system

Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization

Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.</p