Optineurin restrains IL-17-associated neuroinflammation in trigeminal ganglia to preserve sensory function after ocular HSV-1 infection.

Neurotrophic keratitis (NK) arises when trigeminal sensory dysfunction reduces corneal sensation and compromises epithelial maintenance. Herpes simplex virus type 1 (HSV-1) establishes latency in the trigeminal ganglion (TG) and is a common trigger of acquired NK, yet the host programs that determine whether inflamed ganglia recover or degenerate remain poorly defined. Moreover, experimental models that faithfully capture NK-like neuroimmune pathology are limited. Using a murine ocular HSV-1 infection model, we identify optineurin (OPTN) as a key regulator of trigeminal nerve preservation. Optn-/- mice developed severe corneal opacity and rapid, persistent loss of corneal and whisker sensitivity despite comparable corneal viral titers. Droplet-based single-cell RNA sequencing of TGs at 30 days postinfection revealed reduced recovery of peripheral neuronal transcriptomes and coordinated enrichment of chemokine/NF-κB and Th17/IL-17 gene signatures across neurons, endothelial cells, and myeloid/lymphoid populations. Consistent with these transcriptional programs, IL-17 was elevated in Optn-/- TGs at 30 days, whereas the cornea and draining lymph nodes did not exhibit increased IL-17 production early after infection. Neuronal staining demonstrated loss of the synaptic marker SNCG without increased neuronal death, implicating IL-17-associated inflammation in neuronal dysfunction rather than acute ablation. Together, these findings identify OPTN as a neuroimmune checkpoint that restrains chronic IL-17-linked ganglionic inflammation to preserve sensory function and suggest that OPTN deficiency provides a tractable experimental model for studying HSV-associated NK.