Extracellular superoxide dismutase 3 (SOD3) attenuates non-Sjögren and Sjögren syndrome dry eyes in animal models.

Abstract

This study evaluated the effects of superoxide dismutase 3 (SOD3), a known anti-oxidant and anti-inflammatory agent, in both non-Sjögren and Sjögren syndrome (SS) dry eyes in murine models. Dry eyes (DE) were induced in 6-week-old C57BL/6 female mice by extraorbital lacrimal gland excision, and SOD3 or PBS was topically administered once daily for seven days. For SS DE model, NOD/LtJ female mice with developed dry eyes were treated with topical SOD3 or PBS once daily for 14 days. Clinical DE parameters such as tear volume and corneal stain scores, conjunctival goblet cell density, and pro-inflammatory cytokine expressions in cornea and conjunctiva were evaluated in both DE models. In SS DE model, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal gland were also evaluated. Topical SOD3 significantly improved both clinical DE meters and conjunctival goblet cell density in non-SS and SS DE models. Expression of pro-inflammatory cytokines in the cornea and conjunctiva was reduced considerably in both DE models. Interestingly, the infiltration of inflammatory foci and B cells and the expression of hyperactivated autophagy markers in the lacrimal gland were decreased in SS murine model treated with topical SOD3. This study demonstrates, for the first time, that topical SOD3 improved dry eyes in both non-SS and SS murine models and might be used as a potential therapeutic agent.