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Comparison of Aqueous and Vitreous Lymphocyte Populations From Two Rat Models of Experimental Uveitis.

ABSTRACT: Purpose:To compare lymphocyte populations present within inflamed eyes in two rat models of autoimmune uveitis. Methods:Experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU) were initiated in Lewis rats. Aqueous and vitreous were collected at peak inflammation (PMU at day 2, EAU at day 14). The number of cells in the aqueous and vitreous was determined and compared for each eye and between the two models. Intraocular CD-19+ B cells, CD3+ T cells, and CD4+ or CD8+ T-cell subpopulations were identified by flow cytometry and compared between EAU and PMU. Results:The median number of cells/mL collected from PMU aqueous (7.98 × 107 cells/mL), was not significantly different from the number of cells collected from EAU aqueous (1.61 × 107 cells/mL, P = 0.94). EAU aqueous contains a significantly larger mononuclear population (median 61%, interquartile range [IQR] 44%-67%) than PMU (median 9%, IQR 8%-10% [P < 0.0001]). Within the mononuclear population, EAU and PMU aqueous demonstrate similar proportions of CD3+, CD4+ T cells. However, EAU has a larger CD3+, CD8+, T-cell population than PMU, and this population also demonstrates co-expression of CD45R. B cells comprise a significantly larger median percentage of cells in EAU aqueous (median 18%, IQR 15%-20%) compared to PMU (median 13%, IQR 9%-15%, P = 0.006). Conclusions:Flow cytometry analysis of intraocular lymphocytes from EAU and PMU identifies similarities and differences between the T-cell and B-cell populations present at peak inflammation. Complementary animal models that have well-defined mechanistic differences will improve our ability to test potential new therapies and bring meaningful advances into clinical practice for patients with uveitis.

SUBMITTER: Pepple KL

PROVIDER: S-EPMC5963002 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Comparison of Aqueous and Vitreous Lymphocyte Populations From Two Rat Models of Experimental Uveitis.

Pepple Kathryn L KL Wilson Leslie L Van Gelder Russell N RN

Investigative ophthalmology & visual science 20180501 6

<h4>Purpose</h4>To compare lymphocyte populations present within inflamed eyes in two rat models of autoimmune uveitis.<h4>Methods</h4>Experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU) were initiated in Lewis rats. Aqueous and vitreous were collected at peak inflammation (PMU at day 2, EAU at day 14). The number of cells in the aqueous and vitreous was determined and compared for each eye and between the two models. Intraocular CD-19+ B cells, CD3+ T cells, and CD4+ or ...[more]

PMID: 29847657

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Project description:A major limitation of most animal models of autoimmune diseases is that they do not reproduce the chronic or relapsing-remitting pattern characteristic of many human autoimmune diseases. This problem has been overcome in our rat models of experimentally induced monophasic or relapsing-remitting autoimmune uveitis (EAU), which depend on the inducing antigen peptides from retinal S-Antigen (monophasic EAU) or interphotoreceptor retinoid-binding protein (relapsing EAU). These models enable us to compare autoreactive and regulatory T cell populations. Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN-?, IL-17 and IL-10) at distinct time points during monophasic or relapsing EAU. Only intraocular T cells concomitantly produced IFN-?, IL-17 and/or IL-10. Monophasic EAU presented rising numbers of cells expressing IFN-? and IL-17 (Th1/Th17) and cells expressing IL-10 or Foxp3. During relapsing uveitis an increase of intraocular IFN-?+ cells and a concomitant decrease of IL-17+ cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and cells expressing IL-10, even in combination with IFN-? or IL-17, increased during the resolution of monophasic EAU, suggesting a regulatory role for these T cells. In general, cells producing multiple cytokines increased in monophasic and decreased in relapsing EAU. The distinct appearance of certain intraocular populations with characteristics of regulatory cells points to a differential influence of the ocular environment on T cells that induce acute and monophasic or relapsing disease. Here we provide evidence that different autoantigens can elicit distinct and differently regulated immune responses. IFN-?, but not IL-17 seems to be the key player in relapsing-remitting uveitis, as shown by increased, synchronized relapses after intraocular application of IFN-?. We demonstrated dynamic changes of the cytokine pattern during monophasic and relapsing-remitting disease with strongly increasing IL-10 expression in intraocular T cells during monophasic uveitis.

Project description:BackgroundAnimal trials contribute to major achievements in medical science. The so-called lavage model is frequently used to evaluate ventilation strategies in acute respiratory distress syndrome (ARDS) using electrical impedance tomography (EIT). But, the lavage model itself might have systematic impacts on EIT parameters. Therefore, we established an additional experimental model, in which ARDS is caused by intravenously administered lipopolysaccharide (LPS). In this study, we want to examine if EIT measurements provide consistent results in both experimental models or whether the pathophysiology of the model influences the findings. Overall, we want to compare both experimental models regarding clinical parameters and EIT-derived indices, namely the global inhomogeneity (GI) index and the regional ventilation delay (RVD) index.MethodsNineteen pigs were included in this study, allocated to the control group (CO; n = 5), lavage group (LAV; n = 7) and LPS group (LPS; n = 7). After baseline measurements and the establishment of ARDS, assessment of respiratory mechanics, hemodynamics, gas exchange and EIT recordings were performed hourly over eight hours.ResultsIn both experimental ARDS models, EIT measurements provided reliable results. But, the GI and the RVD index did not show consistent results as compared to the CO group. Initially, GI and RVD index were higher in the LAV group but not in the LPS group as compared to the CO group. This effect disappeared during the study. Furthermore, the GI index and the RVD index were higher in the LAV group compared to the LPS group in the beginning as well. This, once again, disappeared. Clinical lung injury parameters remained more stable when using LPS.ConclusionThe two models showed quite different influences on the GI and RVD index. This implies, that the underlying pathophysiology affects EIT parameters and thus the findings. Hence, translation to EIT-guided clinical therapy in humans suffering from ARDS might be limited.

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Comparison of Aqueous and Vitreous Lymphocyte Populations From Two Rat Models of Experimental Uveitis.

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Comparison of Aqueous and Vitreous Lymphocyte Populations From Two Rat Models of Experimental Uveitis.

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