Figure 2.

Mice treated with i35-Exosomes are protected from developing severe EAU. EAU was induced in C57BL/6J mice by immunization with the uveitogenic peptide, IRBP_651−670 in CFA and effect of treatment with PBS or i35-Exosomes on EAU progression was assessed by fundoscopy, histology, optical coherence tomography (OCT), and electroretinography (ERG). (A) Scheme used for exosome treatment. (B) Fundus image of the retina was taken at day 15 or 17 after EAU induction using an otoendoscopic imaging system. Compared to mice treated with i35-Exosomes, fundus images of mice treated with PBS revealed more severe ocular inflammation characterized by significant blurring of the optic disc margins and enlarged juxtapupillary area (black arrow), retinal vasculitis (blue arrows), yellow-whitish retinal and choroidal infiltrates (white arrow). Clinical scores and assessment of disease severity were based on changes at the optic nerve disc or retinal vessels and retinal and choroidal infiltrates. Histogram to the right shows the clinical scores (n = 14). (C) Histologic images. Eyes show very severe EAU in mice treated with PBS as characterized by the development massive retinal in-folding (*), a hallmark feature of severe uveitis. H&E histological sections: Scale bar, 100 μm. V, vitreous; GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer; RPE/CH retinal pigmented epithelial and choroid. Blue arrows, lymphocytes; Asterisks, retinal-folds. (D) Representative OCT images show marked decrease of inflammatory cells (white arrows) in the vitreous and optic nerve head of mice treated with i35-Exosomes (white arrows) (E) ERG analysis of the retina on day-17 after EAU induction. The averages of light- or dark-adapted ERG a-wave or b-wave amplitudes are plotted as a function of flash luminance and values are means ± SEM. Data are presented as the mean ± SEM of at least three determinations. Results represent three independent studies. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.