Somatostatin Ameliorates Corneal Nerve Abnormalities and Inflammation Through Regulation of Macrophage Activities in Dry Eye Disease.

Purpose: This study aimed to investigate the therapeutic effects of pasireotide (SOM230) on corneal nerve abnormalities in a mouse model of dry eye disease (DED) and to elucidate its potential mechanisms of action. Methods: Male C57BL/6J mice underwent lacrimal gland excision (LGE) to induce DED and were treated with SOM230 or PBS. Corneal epithelial integrity, pain-related behaviors, and corneal sensitivity were evaluated. RNA sequencing was performed to identify potential pathways modulated by SOM230. Flow cytometry and immunofluorescence quantified macrophage polarization states. Results: SOM230 treatment significantly improved corneal epithelial integrity, reduced pain behaviors, and restored corneal sensitivity compared to PBS. RNA sequencing revealed that SOM230 downregulated key inflammatory pathways, including TNF-α and NF-κB. Flow cytometry and immunofluorescence showed that SOM230 modulated macrophage polarization by decreasing pro-inflammatory M1 macrophages and enhancing anti-inflammatory M2 macrophages, contributing to reduced corneal inflammation and improved healing. Conclusions: SOM230 alleviates nerve abnormalities in DED by suppressing inflammatory pathways (TNF-α, NF-κB) and promoting a shift in macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. These findings suggest that modulation of macrophage polarization is a crucial mechanism underlying the therapeutic effects of SOM230, highlighting its potential as a treatment strategy for nerve damage in DED.