Abstract
Purpose :
Chronic ocular pain is a prevalent symptom of dry eye disease (DED), chemical burns, infectious keratitis, and corneal surgical procedures, predominately by showing increased pain perception and eye discomfort. Purinergic receptor P2X4 is present on the ocular surface, the trigeminal neurons, and microglia cells. In this study, we aimed to explore the therapeutic potential of a P2X4R antagonist Bay293 to treat ocular neuropathic pain.
Methods :
Ocular neuropathic pain was induced by double lacrimal gland removal (DLGR) in Sprague-Dawley rats (age 8-9 weeks, male, n=12/group). Two weeks after the surgery (post-surgery), we divided the animals into three groups: vehicle, 0.05% cyclosporine ophthalmic emulsion, and Bay293 in vehicle at 2.5mg/ml. Each animal was treated with two eyedrops twice a day for 4 weeks. Blink tests, wipe test, and in vivo confocal microscope (IVCM) images were acquired at pre-surgery, post-surgery, 2 weeks and 4 weeks post-surgery. The density of the corneal subbasal nerve plexus (SNP) and inflammatory cells was counted. One-way ANOVA was used to assess differences among groups and the student’s t-test was used to detect statistical difference between groups.
Results :
Our result showed an increase in both the wipe test and blink test following surgery, correlating with higher SNP density and inflammation cell density after DLGR model establishment. Bay293 at 2.5 mg/ml reduced the wipe and blink test 2 and 4 weeks after the treatment compared to the vehicle (p<0.01). IVCM showed that Bay293 ameliorated the increase of SNP and inflammatory cell density after the DLGR (p<0.01). Bay293 at 2.5mg/ml had a comparable effect to a 0.05% cyclosporine ophthalmic emulsion in reducing wipe test and inflammatory cells density. Cyclosporine shows no effects in the blink test compared to the vehicle, but it further reduced SNP density compared to Bay293 (p<0.05). It showed that Bay293 work though the neuro-modulator pathway to reduce the neuropathic pain similar to cyclosporine.
Conclusions :
P2X4 antagonist Bay293 decreased the discomfort perception and enhanced eye comfort, offering a valuable alternative to chronic ocular discomfort management alongside cyclosporine.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.