THBS1 inhibition alleviates inflammatory response by inhibiting TGF-β and NLRP3 inflammasome in experimental murine dry eye

Dry eye is a multifactorial ocular surface disease that may be accompanied by visual impairment and ocular surface damage. Thrombospondin 1 (THBS1) was found to be highly expressed in corneal epithelial cells of dry eye mouse models. Our research aimed at exploring the role and regulatory mechanism of THBS1 in dry eye mouse models. Both eyes of mice with benzalkonium chloride (BAC)-induced dry eye were subconjunctivally injected with the recombinant adeno-associated virus (AAV) vector containing the THBS1 silencing plasmid. Under a slit lamp biomicroscope, the conjunctival irritation including edema, hyperemia, and secretion was scored. Fluorescein staining was performed to evaluate corneal epithelial damage. The conjunctiva tissues were obtained for ELISA, RT-qPCR, histological staining, and western blotting. Dry eye model mice exhibited severe ocular surface damage, reduced tear secretion, conjunctival goblet cell loss, increased conjunctival inflammation, elevated THBS1 expression, and the TGF-β/NLRP3 inflammasome pathway activation. THBS1 silencing ameliorated ocular surface damage, increased tear secretion, attenuated conjunctival goblet cell loss, mitigated conjunctival inflammation, and repressed the TGF-β/NLRP3 inflammasome pathway activation in dry eye mice. THBS1 silencing protects mice against dry eye by inhibiting TGF-β/NLRP3 inflammasome-mediated inflammatory response.