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Adrianna Latuszek, Ming Yuan, Ying Hu, George D. Yancopoulos, Stanley J Wiegand, Jingtai Cao, Carl Romano; Efficacy of an IL-6R antibody in a novel murine dry eye model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4491.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of the present study was to develop a clinically relevant mouse dry eye model, combining aqueous tear deficiency and local cornea inflammation. Furthermore, we evaluated the efficacy of an antibody (Ab) directed towards mouse IL-6R in this model.
For model development, adult, male C57BL/6 mice (Taconic labs) were randomized to naive, sham, benzalkonium chloride (BAC), scopolamine (SCOP) or BAC plus SCOP groups. For SCOP, mice were subcutaneously implanted with osmotic mini-pump filled with SCOP (delivering 2mg/20g B.W./day) lasting for 4 weeks. For BAC, 1ul 0.2% BAC was administered topically to the right eye, B.I.D, 2 days/week. For Ab treatment, mice received BAC plus SCOP, and either anti-mIL6R (10, 35 or 100 mg/kg) or mouse IgG2a Fc control (mFc, 33.3mg/kg) subcutaneously administered twice/week for 4 weeks. Tear production and corneal fluorescein staining were measured every week. On day 28, animals were euthanized. Corneal angiogenesis and lymphangiogenesis were also quantified.
BAC plus SCOP provided a robust dry eye syndrome. Tear production was inhibited by more than 50% (in both SCOP groups, as expected). Corneal fluorescein staining was significantly increased compared to other groups (p<0.001). Corneal angiogenesis and lymphangiogenesis were also significantly increased in this dry eye model. Interestingly, lymphangiogensis but not angiogenesis was significantly correlated with corneal fluorescein staining (p<0.01). We then evaluated the effect of an antibody to IL-6R in this model. Anti-IL-6R treatment has no significant effect on body weight or tear production. However, compared with mFc, anti-IL-6R treatment dose-dependently and significantly decreased both corneal fluorescein staining (30% reduction with 100mg/kg) and associated lymphangiogenesis (50% reduction with 100mg/kg) at 4 weeks.
We have established a novel dry eye model with reduced tear secretion and enhanced damage, angiogenesis, and lymphangiogenesis in cornea. Systemic administration of IL-6R antibody alleviated the corneal damage. Anti-IL-6R treatment is a potential therapeutic strategy in dry eye disease.
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