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Molecular mimicry: uveitis induced in Macaca fascicularis by microbial protein having sequence homology with retinal
V K Singh1, J Usukura, T Shinohara
1Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892.
Abstract:
S-antigen (S-Ag), a well characterized 45-kDa protein in the photoreceptor cells, induces predominantly T-cell-mediated autoimmune uveitis when injected into experimental animals. Recently, we have shown that native histone H3 protein derived from yeast (Saccharomyces cerevisiae), or a synthetic peptide that is homologous with S-Ag peptide M in having six consecutive amino acids, induces experimental autoimmune uveitis (EAU) similar to that induced by native S-Ag in the Lewis rat. In this study, monkeys (Macaca fascicularis) immunized with histone H3 peptide developed a strong cellular immune response to this peptide as well as to peptide M. However, no significant inflammation or hypervascularization was observed in the retina or the iris during the experimental period, when they were examined clinically with an inverted ophthalmoscope. Histopathological examination showed that all monkeys injected with histone H3 peptide or with native histone H3 lost a large number of photoreceptor rod cells and developed neovascularization in the outer nuclear cell layer of the retina. These histopathological findings in the monkey retina closely resemble those seen in human patients with some types of uveitis. The possible involvement of microbial proteins having sequence homology with normal retinal proteins in the pathogenicity of human uveitis is discussed.
Insights
Histone H3 peptide can trigger autoimmune uveitis in monkeys, causing photoreceptor cell loss and retinal neovascularization. This finding suggests potential links between microbial proteins and human uveitis.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- S-antigen (S-Ag) is a photoreceptor protein that induces T-cell-mediated autoimmune uveitis.
- Previous studies showed yeast-derived histone H3 or a homologous peptide can induce experimental autoimmune uveitis (EAU) in rats.
Purpose of the Study:
- To investigate the effects of histone H3 peptide immunization on non-human primates (Macaca fascicularis).
- To evaluate the potential of histone H3 peptide as an animal model for human uveitis.
Main Methods:
- Monkeys were immunized with histone H3 peptide.
- Immune responses were assessed, and ocular tissues were examined clinically and histopathologically.
- Clinical examination included inverted ophthalmoscopy.
Main Results:
- Histone H3 peptide immunization induced a strong cellular immune response to the peptide and S-Ag peptide M.
- No significant clinical inflammation or hypervascularization was observed.
- Histopathology revealed substantial photoreceptor rod cell loss and retinal neovascularization in the outer nuclear layer.
Conclusions:
- Histone H3 peptide induces significant retinal pathology in monkeys, mimicking human uveitis.
- This model may be valuable for studying the pathogenesis of human uveitis.
- The study discusses the potential role of microbial proteins with sequence homology to retinal proteins in human uveitis.