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Jian Li, Jia Lin Ren, Wong Ying Yip, Xiao Yu Zhang, SUNON CHAN, WAI KIT CHU, Chi Pui Calvin Pang; Establishment and characterization of hIRBP-induced experimental autoimmune uveoretinitis in mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3306.
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© ARVO (1962-2015); The Authors (2016-present)
Human interphotoreceptor retinoid-binding protein (hIRBP) induced experimental autoimmune uveoretinitis (EAU) in mice has been used to study autoimmune inflammatory eye diseases. Characterization of ocular changes in living animals with EAU is essential for longitudinal follow-ups and experimental studies. Thus, we conducted longitudinal assessments of ocular pathological and functional changes in EAU mice using non-invasive techniques.
hIRBP was subcutaneously injected into 6 weeks old female C57BL/6J mice at 300 μg/mouse (N=3). Control animals were given normal saline (N=3). At 6 time points during a 21-day experimental period, the eyes were examined by slit lamp microscopy, confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments. Retinal thicknesses in specific regions around the optic nerve were measured in OCT images. FFA images were used to determine diameters of the major retinal vessel in each eye. Mann-Whitney test was used for statistical analysis.
EAU was induced in all mice in hIRBP injected group. On Day 14 after hIRBP injection, cellular infiltration in the vitreous, retinal vasculitis and edema were observed in the OCT images, which were correlated with observations from images of cSLO, FFA and histological sections. ERG showed reductions in both scotopic and photopic a- and b-wave amplitudes on Day 21 after immunization, indicating the inflammation had caused functional disruptions in vision. Slit lamp microscopy did not show obvious inflammation in the anterior chamber. The fold change of retinal thickness on Day 21 after immunization in hIRBP injected mice (1.04±0.01) increased significantly when compared to control mice (0.99±0.02, p=0.021), indicating retinal edema during EAU. Major retinal vascular diameter in hIRBP injected animals (377.33±15.56 unit) was also increased compared to control animals (295.33±7.78 unit, p=0.004), demonstrating the vasodilatation as a result of EAU.
hIRBP-induced autoimmune ocular inflammation in mice can be assessed reliably by in vivo monitoring using OCT, cSLO, FFA and ERG. ERG amplitude, retinal thickness and vascular diameter provide quantifiable indicators, which allow reproducible evaluations of autoimmune ocular inflammation in longitudinal studies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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