Evaluation of mouse experimental autoimmune uveoretinitis by spectral domain optical coherence tomography

Harimoto, Kohzou; Ito, Masataka; Kobayashi, Yôko; Sakurai, Yoshinori; Takeuchi, Masaru

doi:10.1136/bjophthalmol-2013-304421

Cited by 25 publications

(31 citation statements)

References 19 publications

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“…Funduscopic and OCT examinations were conducted on days 7, 14, and 21 postimmunization, and histological and FA examinations were conducted on day 21. Clinical scores [4] and OCT scores [19] were calculated as previously described. Splenocytes were harvested from EAU mice for flow cytometry analyses or to evaluate IRBP-induced cytokine production by retinal antigen-specific T cells in vitro.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3 antibody

et al. 2017

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BackgroundA novel anti-mouse CD3ε antibody, Dow2, recognizes mouse CD3ε without activating T cells and suppresses T-cell activation. The purpose of this study was to determine whether Dow2 can inhibit T cells in uveitis.MethodsExperimental autoimmune uveitis (EAU) was induced in mice by immunization with retinal peptides, followed by administration of Dow2. Inflammation was evaluated by color fundus photography, optical coherence tomography, fluorescein angiography, and histology. Intraocular cells from EAU mice were used to examine the effect of Dow2 on retinal antigen-specific T cells. The effects of Dow2, conventional CD3ε antibodies, and isotype control immunoglobulin G (IgG) on splenic T cells were compared by assessing cell proliferation by the mixed lymphocyte reaction assay, inflammatory cytokine production by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, and gene expression by quantitative reverse-transcription polymerase chain reaction (RT-PCR). T-cell subpopulations were characterized by flow cytometry to evaluate the expression of CD4, CD8, CD44, CD62L, and Foxp3.ResultsDow2 significantly reduced T-cell activation and counteracted activation associated with anti-CD3ε antibodies. Unlike conventional CD3ε antibodies, Dow2 treatment did not upregulate T helper (Th)1-/Th17-associated gene expression and cytokine production in splenic T cells. Interferon (IFN)-γ production by retinal antigen-specific T cells was also significantly reduced. Ocular inflammation was significantly reduced in Dow2-treated EAU mice compared to control EAU mice, with fewer T cells infiltrating into the retinas of Dow2-treated EAU mice. In immunohistochemistry, Th1 and Th17 cells invaded the retina in control EAU mice but not Dow2-treated EAU mice. No effects on peripheral T-cell numbers were observed following systemic administration of Dow2.ConclusionThe novel anti-CD3 antibody Dow2 can inhibit T cell-mediated inflammation in uveitis models. Thus, inhibition of T-cell activation by anti-CD3 therapy with this new antibody may protect uveitis patients from severe ocular inflammation.

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Section: Methodsmentioning

confidence: 99%

Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3 antibody

et al. 2017

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“…[20][21][22][23] The results indicate that OCT could become an effective assay tool for the longitudinal monitoring of pathological changes in the retinal lesions during uveitis. [20][21][22][23] In this paper, we report a new application of OCT and OCTbased microangiography (OMAG) [24][25][26][27][28] to a rodent model of anterior uveitis. Acute anterior uveitis (AAU) is the commonest form of uveitis with single episodes of sudden onset and limited duration, involving the inflammation of the AC, iris, and CB.…”

Section: Introductionmentioning

confidence: 90%

Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitisin vivo: a preliminary study

et al. 2015

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Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/ OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

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“…5,19,24–29 Optical coherence tomography-based systems have the benefit of providing high-resolution structural images that are amiable to automated quantitative analysis 14,19,24 or that can be combined with in vivo imaging of fluorescently labeled ocular structures in transgenic mice. 30 However, media opacity generated by ocular inflammation (corneal edema, cataract, hypopyon, vitritis) can degrade OCT image quality and limit quantitative analysis.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis

Gutowski

Wilson

Gelder

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeWe develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis.MethodsThree models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU.ResultsIn the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation.ConclusionsIn vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

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Evaluation of mouse experimental autoimmune uveoretinitis by spectral domain optical coherence tomography

Abstract: SD-OCT is useful for evaluating the development and severity of mouse EAU. The SD-OCT scoring system we developed accurately reflects clinical and histopathological changes.

Cited by 25 publications

References 19 publications

Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3 antibody

Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3 antibody

Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitisin vivo: a preliminary study

In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis

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