Single-Cell Profiling Identifies Glial Transcriptional Remodeling in the Trigeminal Ganglion After Corneal Injury.

The cornea depends on trigeminal sensory innervation for sensation and epithelial homeostasis, yet cell type-specific transcriptional responses in the trigeminal ganglion following corneal injury remain incompletely defined. To address this gap, we combined bulk and single-cell RNA sequencing to profile the mouse trigeminal ganglion after a moderate corneal alkali injury associated with transient denervation and an early phase of nerve regeneration. Corneal injury elicited a robust early transcriptional response dominated by glial populations. In myelinating Schwann cells, injury responses were characterized by transcriptional programs supporting neuronal communication and remodeling of inflammatory signaling, while nonmyelinating Schwann cells and satellite glia showed strong enrichment of proteostasis-related pathways. Single-cell analysis further revealed that neurons responded to injury by downregulating protein translation and mitochondrial activity. In parallel, inference of ligand-receptor interactions indicated that early injury responses involved extensive neuron-glia communication, whereas later responses became more neuron-centered, reflecting a shift toward neuron-derived ligand signaling. Together, these data define a corneal injury-associated transcriptional landscape of the trigeminal ganglion characterized by prominent glial proteostasis responses and a time-dependent reorganization of neuron-glia communication.