Effect of intravitreal injection of anti-interleukin (IL)-6 antibody in experimental autoimmune uveitis in mice

Abstract

Purpose: The aim of this study was to assess the functional and clinical impact of intravitreal administration of a neutralizing anti-IL-6 antibody in the treatment of experimental autoimmune uveitis (EAU) in mice.

Methods: EAU was induced in 17 female B10.RIII mice by administering Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, followed by a boost with Pertussis toxin. Intravitreal injections of anti-Interleukin (IL)-6 antibody were administered on days 10, 13, and 16 after EAU induction (day 0) into the randomized treatment eye, with an isotype antibody similarly injected into the fellow control eye. Visual acuity was assessed using the optomotor reflex via OptoDrum, and clinical scoring was performed via fundus imaging (utilizing 6 EAU grades) in a single-blinded manner on days 0, 10, 13, 16, and 18.

Results: Uveitis developed in all 17 mice. Significantly higher visual acuity was observed in treated eyes compared to control eyes on days 13, 16, and 18. The most pronounced effect was noted on days 16 and 18 (p < 0.001). On days 13, 16, and 18 the number of eyes with lower EAU-score was significantly higher in the treatment group, with the most notable effect observed on day 18 (p < 0.003).

Conclusion: Intravitreal administration of anti-IL-6 treatment notably mitigates experimental autoimmune uveitis in mice, both functionally and clinically. Further investigations are warranted to assess the potential of intravitreal anti-IL-6 therapy as a treatment option for non-infectious uveitis in humans.

Keywords: Experimental autoimmune uveitis; Intravitreal therapy; Non-infectious uveitis; Uveitis; anti-IL-6 antibody.

Fig. 1

Boxplots illustrating EAU score for both the control group (light gray) and the treatment group (dark gray) over the examination days in n = 17 eyes each. The boxplots show the median EAU score, the 25th percentile, the 75th percentile, the interquartile range, as well as the minimum and maximum values. Outliers are also marked separately

Fig. 2

Bar chart depicting absolute frequency of each EAU score according to each group on examination days 10, 13, 16 and 18

Fig. 3

Funduscopy and fluorescein angiography images of a single mouse as an example. Upper row: findings of the control eye treated with the isotype antibody. Bottom row: findings of the eye treated with anti-IL-6 antibody. The days of the study are arranged from left to right. The EAU score is indicated in the upper right corner of each image

Fig. 4

Boxplots illustrating visual acuity for both the control group (light gray) and the treatment group (dark gray) over the examination days in n = 17 animals. The Boxplots show the median visual acuity, the 25th percentile, the 75th percentile, the interquartile range, as well as the minimum and maximum values. Outliers are also marked separately. *p < 0.05, **p < 0.01, *** p < 0.001

Fig. 5

Determining visual acuity based on the EAU score. Representation of the regression line and the regression equation; the points depict the measured visual acuity values in cpd at their respective EAU scores