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Comparative analysis of induced vs. spontaneous models of autoimmune uveitis targeting the interphotoreceptor retinoid binding protein.

Chen J, Qian H, Horai R, Chan CC, Falick Y, Caspi RR - PLoS ONE (2013)

Bottom Line: Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease.Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography.All models were on the B10.RIII background.

View Article: PubMed Central - PubMed

Affiliation: Immunoregulation Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease. We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the "classical" model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)(-/-) mice. Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography. All models were on the B10.RIII background. Unlike previously reported, IRBP-induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: severe monophasic with extensive destruction of the retina and rapid loss of visual signal, or lower grade with a prolonged chronic phase culminating after several months in retinal degeneration and loss of vision. R161H and AIRE(-/-) mice spontaneously developed chronic progressive inflammation; visual function declined gradually as retinal degeneration developed. Spontaneous uveitis in R161H mice was characterized by persistent cellular infiltrates and lymphoid aggregation, whereas AIRE(-/-) mice characteristically developed multi-focal infiltrates and severe choroidal inflammation. These data demonstrate variability and unique distinguishing features in the different models of uveitis, suggesting that each one can represent distinct aspects of uveitis in humans.

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Semi-quantitative evaluation of cellular infiltrates in the vitreous of mice with induced and spontaneous uveitis.A, Longitudinal imaging of volume scan OCT was performed during the course of EAU in the vitreous of the same eyes as in Figure 2. (A,B) IRBP induced EAU (n = 8); (C,D) R161H (n = 8); (E,F) AIRE−/− (n = 6). B, Semi-quantitative evaluation of cellular infiltrates over time. Volume-scan of OCT images was captured in the vitreous (Materials and Methods). All images were digitally processed in the same way using Photoshop to equalize background contrast levels. Signal intensity of OCT volume scan was then measured and analyzed using ImageJ analysis. Data are presented as mean ± SEM of percent increase of OCT intensity to normal or WT mice.
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pone-0072161-g004: Semi-quantitative evaluation of cellular infiltrates in the vitreous of mice with induced and spontaneous uveitis.A, Longitudinal imaging of volume scan OCT was performed during the course of EAU in the vitreous of the same eyes as in Figure 2. (A,B) IRBP induced EAU (n = 8); (C,D) R161H (n = 8); (E,F) AIRE−/− (n = 6). B, Semi-quantitative evaluation of cellular infiltrates over time. Volume-scan of OCT images was captured in the vitreous (Materials and Methods). All images were digitally processed in the same way using Photoshop to equalize background contrast levels. Signal intensity of OCT volume scan was then measured and analyzed using ImageJ analysis. Data are presented as mean ± SEM of percent increase of OCT intensity to normal or WT mice.

Mentions: Vitreous haze and aqueous flare are useful clinical parameters to quantitate inflammation in the patient [23]. In the 3 mouse models, we monitored the kinetics of cellular infiltration into the vitreous with volume-scan OCT images shown in Figure 4 (A,C,E), and semi-quantitatively evaluated the cellular infiltration by processing and measuring OCT signal intensity using ImageJ analysis shown in Figure 4 (B,D,F).


Comparative analysis of induced vs. spontaneous models of autoimmune uveitis targeting the interphotoreceptor retinoid binding protein.

Chen J, Qian H, Horai R, Chan CC, Falick Y, Caspi RR - PLoS ONE (2013)

Semi-quantitative evaluation of cellular infiltrates in the vitreous of mice with induced and spontaneous uveitis.A, Longitudinal imaging of volume scan OCT was performed during the course of EAU in the vitreous of the same eyes as in Figure 2. (A,B) IRBP induced EAU (n = 8); (C,D) R161H (n = 8); (E,F) AIRE−/− (n = 6). B, Semi-quantitative evaluation of cellular infiltrates over time. Volume-scan of OCT images was captured in the vitreous (Materials and Methods). All images were digitally processed in the same way using Photoshop to equalize background contrast levels. Signal intensity of OCT volume scan was then measured and analyzed using ImageJ analysis. Data are presented as mean ± SEM of percent increase of OCT intensity to normal or WT mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756070&req=5

pone-0072161-g004: Semi-quantitative evaluation of cellular infiltrates in the vitreous of mice with induced and spontaneous uveitis.A, Longitudinal imaging of volume scan OCT was performed during the course of EAU in the vitreous of the same eyes as in Figure 2. (A,B) IRBP induced EAU (n = 8); (C,D) R161H (n = 8); (E,F) AIRE−/− (n = 6). B, Semi-quantitative evaluation of cellular infiltrates over time. Volume-scan of OCT images was captured in the vitreous (Materials and Methods). All images were digitally processed in the same way using Photoshop to equalize background contrast levels. Signal intensity of OCT volume scan was then measured and analyzed using ImageJ analysis. Data are presented as mean ± SEM of percent increase of OCT intensity to normal or WT mice.
Mentions: Vitreous haze and aqueous flare are useful clinical parameters to quantitate inflammation in the patient [23]. In the 3 mouse models, we monitored the kinetics of cellular infiltration into the vitreous with volume-scan OCT images shown in Figure 4 (A,C,E), and semi-quantitatively evaluated the cellular infiltration by processing and measuring OCT signal intensity using ImageJ analysis shown in Figure 4 (B,D,F).

Bottom Line: Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease.Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography.All models were on the B10.RIII background.

View Article: PubMed Central - PubMed

Affiliation: Immunoregulation Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease. We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the "classical" model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)(-/-) mice. Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography. All models were on the B10.RIII background. Unlike previously reported, IRBP-induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: severe monophasic with extensive destruction of the retina and rapid loss of visual signal, or lower grade with a prolonged chronic phase culminating after several months in retinal degeneration and loss of vision. R161H and AIRE(-/-) mice spontaneously developed chronic progressive inflammation; visual function declined gradually as retinal degeneration developed. Spontaneous uveitis in R161H mice was characterized by persistent cellular infiltrates and lymphoid aggregation, whereas AIRE(-/-) mice characteristically developed multi-focal infiltrates and severe choroidal inflammation. These data demonstrate variability and unique distinguishing features in the different models of uveitis, suggesting that each one can represent distinct aspects of uveitis in humans.

Show MeSH
Related in: MedlinePlus