TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis.

Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1+ sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1+ sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.

Antibiotic-induced dysbiosis of gut microbiota impairs corneal development in postnatal mice by affecting CCR2 negative macrophage distribution.

Antibiotics are extremely useful, but they can cause adverse impacts on host bodies. We found that antibiotic treatment altered the composition of the gut microbiota and the gene expression profile in the corneal tissues of postnatal mice and decreased the corneal size and thickness, the angiogenesis of limbal blood vessels, and the neurogenesis of corneal nerve fibers. The reconstitution of the gut microbiota with fecal transplants in antibiotic-treated mice largely reversed these impairments in corneal development. Furthermore, C-C chemokine receptor type 2 negative (CCR2-) macrophages were confirmed to participate in corneal development, and their distribution in the cornea was regulated by the gut microbiota. We propose that the CCR2- macrophage population is a crucial mediator through which gut microbiota affect corneal development in postnatal mice. In addition, probiotics were shown to have the potential effect of restoring corneal development in antibiotic-treated mice. Abx-induced gut dysbiosis has significant, long-term effects on the development of the cornea, and reversal of these suppressive effects takes a long time.