Experimental Autoimmune Uveoretinitis in the Rat and Mouse

Abstract

Experimental autoimmune uveoretinitis (EAU) in rats and mice is a prototypic T cell-mediated autoimmune disease that targets the neural retina and related tissues. The model is used to represent human sight-threatening inflammatory eye diseases that are believed to have an autoimmune etiology, and to study basic mechanisms of tolerance and autoimmunity to organ-specific antigens from immunologically privileged sites. In this unit, EAU is induced in rats and mice by immunization with uveitogenic peptide antigens emulsified in complete Freund's adjuvant (CFA). Clinical onset is observed by both external and microscopic examination. A protocol is provided for preparation of tissue sections of affected eyes for microscopic analysis. EAU can also be induced in the rat (as described) by adoptive transfer of lymphocytes from uveitic rats into unimmunized recipients, which obviates the use of CFA. To induce EAU in mice, Bordetella pertussis toxin (PTX) is included to overcome immunological resistance mechanisms.

Longitudinal Intravital Imaging of the Retina Reveals Long-term Dynamics of Immune Infiltration and Its Effects on the Glial Network in Experimental Autoimmune Uveoretinitis, without Evident Signs of Neuronal Dysfunction in the Ganglion Cell Layer

“…In line with previous reports (9, 10, 19), immunofluorescence and histology (HE) analysis of the retina at peak of EAU corroborated our fundoscopy results. As highlighted by DAPI and HE staining in cross sections of the eye, the highly ordered retinal layer structure common to healthy controls becomes wave-shaped (Figure S1C in Supplementary Material) and massive immune cell infiltration was found throughout all retinal layers and in the vitreous humor in the EAU mice, but not in healthy controls.…”

Longitudinal Intravital Imaging of the Retina Reveals Long-term Dynamics of Immune Infiltration and Its Effects on the Glial Network in Experimental Autoimmune Uveoretinitis, without Evident Signs of Neuronal Dysfunction in the Ganglion Cell Layer

“…In line with previous reports (9, 10, 19), immunofluorescence and histology (HE) analysis of the retina at peak of EAU corroborated our fundoscopy results. As highlighted by DAPI and HE staining in cross sections of the eye, the highly ordered retinal layer structure common to healthy controls becomes wave-shaped (Figure S1C in Supplementary Material) and massive immune cell infiltration was found throughout all retinal layers and in the vitreous humor in the EAU mice, but not in healthy controls.…”

A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and its Disruptive Application Efficiency

“…Histopathological results con rmed diffuse in ammatory in ltration of the cornea, uveal, and retina, disorganization in the retinal pigment epithelium and the inner nuclear layer, and retinal folding. Those pathological features in our study can be supported by data available from studies on classical B10RIII mice [11,12], B10.A mice , C57BL/6J mice with EAU [14], and human uveitis [15]. Those results suggest that the tree shrew EAU model in the present study can represent human uveitis and previously reported classical EAU in mice.…”

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

“…Focal retinal destruction occurred at the end of the acute phase, followed by chronic retinal inflammation persisting for more than 1 mo (data not shown). Interestingly, similar pathological features and kinetics of ocular inflammation have been observed in previously described models of autoimmune uveitis (24). Additionally, similar clinical signs of uveitis were observed in our model, whether the target Ag was diffusely expressed in the internal retina (intravitreal injection) or focally expressed in the external retina (subretinal injection).…”

Longitudinal Intravital Imaging of the Retina Reveals Long-term Dynamics of Immune Infiltration and Its Effects on the Glial Network in Experimental Autoimmune Uveoretinitis, without Evident Signs of Neuronal Dysfunction in the Ganglion Cell Layer

“…In line with previous reports (9, 10, 19), immunofluorescence and histology (HE) analysis of the retina at peak of EAU corroborated our fundoscopy results. As highlighted by DAPI and HE staining in cross sections of the eye, the highly ordered retinal layer structure common to healthy controls becomes wave-shaped (Figure S1C in Supplementary Material) and massive immune cell infiltration was found throughout all retinal layers and in the vitreous humor in the EAU mice, but not in healthy controls.…”

A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and its Disruptive Application Efficiency

“…Histopathological results con rmed diffuse in ammatory in ltration of the cornea, uveal, and retina, disorganization in the retinal pigment epithelium and the inner nuclear layer, and retinal folding. Those pathological features in our study can be supported by data available from studies on classical B10RIII mice [11,12], B10.A mice , C57BL/6J mice with EAU [14], and human uveitis [15]. Those results suggest that the tree shrew EAU model in the present study can represent human uveitis and previously reported classical EAU in mice.…”

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

“…Focal retinal destruction occurred at the end of the acute phase, followed by chronic retinal inflammation persisting for more than 1 mo (data not shown). Interestingly, similar pathological features and kinetics of ocular inflammation have been observed in previously described models of autoimmune uveitis (24). Additionally, similar clinical signs of uveitis were observed in our model, whether the target Ag was diffusely expressed in the internal retina (intravitreal injection) or focally expressed in the external retina (subretinal injection).…”

Longitudinal Intravital Imaging of the Retina Reveals Long-term Dynamics of Immune Infiltration and Its Effects on the Glial Network in Experimental Autoimmune Uveoretinitis, without Evident Signs of Neuronal Dysfunction in the Ganglion Cell Layer

“…In line with previous reports (9, 10, 19), immunofluorescence and histology (HE) analysis of the retina at peak of EAU corroborated our fundoscopy results. As highlighted by DAPI and HE staining in cross sections of the eye, the highly ordered retinal layer structure common to healthy controls becomes wave-shaped (Figure S1C in Supplementary Material) and massive immune cell infiltration was found throughout all retinal layers and in the vitreous humor in the EAU mice, but not in healthy controls.…”

A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and its Disruptive Application Efficiency

“…Histopathological results con rmed diffuse in ammatory in ltration of the cornea, uveal, and retina, disorganization in the retinal pigment epithelium and the inner nuclear layer, and retinal folding. Those pathological features in our study can be supported by data available from studies on classical B10RIII mice [11,12], B10.A mice , C57BL/6J mice with EAU [14], and human uveitis [15]. Those results suggest that the tree shrew EAU model in the present study can represent human uveitis and previously reported classical EAU in mice.…”

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

“…Focal retinal destruction occurred at the end of the acute phase, followed by chronic retinal inflammation persisting for more than 1 mo (data not shown). Interestingly, similar pathological features and kinetics of ocular inflammation have been observed in previously described models of autoimmune uveitis (24). Additionally, similar clinical signs of uveitis were observed in our model, whether the target Ag was diffusely expressed in the internal retina (intravitreal injection) or focally expressed in the external retina (subretinal injection).…”