Pergolide is comparable to nerve growth factor in recovery after alkali trauma in mouse corneas

Abstract

Purpose : Corneal nerve injury is a significant clinical challenge after a chemical burn. Existing treatments are unsatisfactory, for example, nerve growth factor (NGF) is difficult to obtain and very expensive. We previously showed that pergolide upregulates NGF and corneal nerve regeneration in an epithelial scratch mouse model. We hypothesized that topical pergolide can alleviate pain and improve corneal nerve regeneration after chemical injury with alkali burn.

Methods : Alkali (0.75 M NaOH) injury was performed on the cornea of 1 eye per mouse (C57BL/6J, 5 males and 5 females per group). Mice were then given eye drops (10 µl) in the injured eye 3 times daily for 3 weeks; pergolide (600, 300, or 50 µg/ml as solution dissolved in a Marinosolv formulation), vehicle (Marinosolv only), or NGF (100 µg/ml). No treatment (injury only) and naïve (no injury/no treatment) groups did not receive drops. Pain behavior was tested weekly with the wiping test; corneal haze grading and body weight changes were assessed at 3 weeks. Heart and eye globes were collected at 3 weeks and corneal nerve fiber regeneration was assessed with corneal flatmount antibody staining (anti-beta 3 tubulin).

Results : In the wiping test, 300 and 600 µg/ml pergolide and NGF groups showed increased wiping compared to baseline (P<0.05), while pergolide 50 µg/ml and negative control groups did not show any change. This was observed at 3 weeks for males and 2 weeks for females. Haze was reduced in the 600 µg/ml pergolide and NGF groups compared to no treatment (P<0.05). Epithelial nerve fiber density in the 300 and 600 µg/ml pergolide and NGF groups was higher than in negative controls (P<0.05). Pergolide 50 µg/ml was not effective in reducing haze or improving nerve density. No weight loss, cardiac or retinal abnormalities were observed.

Conclusions : Increased wiping behavior aligns with NGF treatment, where patients report pain during reinnervation of the cornea. Improvement in haze highlights the relationship between the corneal nerve, stromal, and epithelial cells, and their countercurrent exchange of factors. Behavioral response discrepancy between sexes without differences in other metrics may be related to pain processing. The results confirm our hypothesis that topical pergolide can improve corneal nerve regeneration in structure and function similar to NGF and supports further investigations.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.