The mechanisms underlying ocular pain initiated by blue light stress

Abstract

Purpose : Ocular pain (OP) causes significant morbidity and negatively impacts the quality of life for millions in the United States. However, despite an increased recognition of the importance and prevalence of OP, its diagnosis and management remain challenging because of a lack of understanding regarding the mechanisms underlying OP. We sought to establish a blue light exposure animal model that recapitulates the features of human OP.

Methods : Eight-week-old C57BL/6 mice were reared in cycles of 12-hour of blue light (BL) with 420nm wavelength alternating with 12-hour of darkness . Control mice will be maintained in 12 light/12 dark cycle from white light sources. The changes of behavior were assessed by wind, cold, and chemical stimulation. Corneas or trigeminal ganglion were collected, and immunostaining were performed for tunnel staining, β3-tubutin, SP, TRPV4 or TRPV1. Expression of TRPV1, TRPV4, galanin and SP in corneal projecting neurons (CPNs) were assessed using qPCR.

Results : We discovered that BL-exposure induces hypotonic/hypertonic-induced eye-wiping and decrease tear secretion and stability after cycle 1. The cold-stimulated blinking and wind-stimulated eye-closing behaviors required 3 cycles and their intensities further increased between cycle 7 and 9. Whol e mount confocal microscopy revealed that BL exposure reduced the number of branching of stromal nerve fibers and decreased the density of epithelial nerve endings with increased tortuosity and beadlike fibers/endings. Using neuronal retrograde tracer, the CPNs were identified and most CPNs are both TRPV1 and 4 positive. BL exposure increased the TRPV1 (TRPV1^high), but not TRPV4 staining intensity, particularly in some TRPV4 positive CPNs. The CPN enriched TG fraction had significantly elevated mRNA expression of TRPV1, but not TRPV4, as well as neuropeptides, substance P (SP), CNTFRα and NGFR. At the protein levels, certain TRPV1^high CPNs are also SP positive in the TG and more SP positive nerve endings in the corneas of BL exposed mice.

Conclusions : Taken together, we established a mouse ONP model suitable for studying mechanisms underlying the pathogenesis and chronicity of OP and showed that BL exposure increases TRPV1 and SP expression in the TG and SP secretion, resulting in the sensitization of nociception and ONP.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.