Abstract
Purpose :
The purpose of the study was to evaluate the ability of OK-101, a novel chemerin receptor agonist, to improve neuropathic corneal pain (NCP). We investigated the efficacy of lipidated (L) and non-lipidated (NL) OK-101 in an NCP mouse model of ciliary nerve ligation.
Methods :
NCP was induced by ligation of the ciliary nerve and confirmed by stimulation with 5M hyperosmolar saline (HS) and eye wiping response (counts/30 sec) on day 3. The integrity of the corneal epithelium was revealed by corneal fluorescein staining (CFS, Grade 0-3 in 5 regions on a 0-15 severity scale). Mice were divided into groups and given either L- or NL-OK-101 with a frequency of either 6/6 or 3/6 times/day or balanced salt solution (BSS) vehicle control. Gabapentin (100mg/kg i.p.) given on days 4, 7, 10 and 14 after surgery was used as a positive control. Treatment duration was for a total 11 days and efficacy measured by 5M HS and eye wiping. Safety measures included blink reflex due to mechanical stimulation by Cochet-Bonnet esthesiometer and CFS performed at 7, 10 and 14 days post surgery.
Results :
NCP was established as demonstrated by increased eye wipes after ligation compared to naïve mice (36.65±6.45 vs. 13.74±3.18 counts/30 sec; p<0.0001) with no difference in CFS (p>0.05). Both compounds at either frequency did show an analgesic effect by inhibiting the hypersensitivity to 5M HS compared to BSS at day 14 (L-OK-101 at 3/6 17.5±0.78 and 6/6 15.4±0.73; NL-OK-101 at 3/6 16.8±0.88 and 6/6 14.6±0.75 vs. BSS 27.2±0.68 counts/30 sec; p<0.0001). Additionally, L- and NL-OK-101 at 6/6 and NL-OK-101at 3/6 times per day inhibited corneal nociceptor sensitization similar to gabapentin at day 14 (14.6±0.75, 15.4±0.73 and 16.8±0.88 vs 13.2±0.80 counts/30 sec, respectively). Both L- and NL-OK-101 at either frequency showed statistically significant (p <0.05) recovery of mechanical sensitivity threshold on par with gabapentin and significantly better than vehicle control (p <0.01) at days 7 and 10. Both the compounds showed no effect on corneal epithelial integrity compared to gabapentin or BSS (0.56±0.45 vs. 0.78±0.60 or 0.66±0.50 on the severity scale).
Conclusions :
Topically administered OK-101 was effective in reducing NCP in a ciliary nerve ligation mouse model suggesting OK-101 could be a potential therapeutic target for the treatment of neuropathic corneal pain.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.