The Effect of Blocking Substance P in Treating the Allergic Red Eye

Abstract

Purpose : Allergic conjunctivitis and various conditions can cause conjunctival vessel dialation, leading to ocular redness (OR). Using an animal model of allergic OR, we evaluated the therapeutic efficacy of topical blockade of substance P (SP), which preferentially binds to neurokinin-1 receptor (NK1R) , in treating red eye.

Methods : Allergic OR was induced in guinea pigs with topical 1.5 mg/mL histamine. NK1R antagonist, L-703,606, was applied 10 minutes before or after OR induction as pre-induction or post-induction treatment, respectively. Animal eyes were imaged by a slit lamp (N= 12/group) every 30 seconds in the first 2 minutes, and at 6, 10, 20, 30, 40, 50, and 60 minutes. The redness was analyzed using the ocular redness index (ORI), a score between 0 to 100. After 60 minutes, tear fluid was collected to quantify SP levels by ELSIA (N= 6/group). Lastly, conjunctiva were harvested and stained with H&E to quantify the size of blood vessels and eosinophil and neutrophil infiltration (N= 6/group).

Results : With histamine induction, the ORI peaked at 10 minutes (maximum ORI: 17.04±0.99). Topical treatment of L-703,606 significantly (P<0.05) reduced ORI (pre-induction: 7.38±0.71; post-induction: 10.91±0.59). Compared to naive guinea pigs, histamine increased the conjunctival blood vessel diameter nearly three times (naive: 10.15±1.41; histamine: 30.66±4.12). Both pre- and post-induction treatment decreased blood vessels diameter (pre-induction: 16.84±2.21; post-induction: 23.69±2.36) but only pre-induction had significant (P<0.05) change. The tear concentration of SP was 71.64±19.16 pg/mL in the naive group, and 270.60±38.04 pg/mL in histamine-induced group. Pre-induction treatment significantly (P<0.05) decreased SP concentrations to 154.10±9.72 pg/mL and post-induction treatment lowered SP levels to 191.10±13.52 pg/mL. The numbers of eosinophils and neutrophils were 8.50±2.69 and 4.67±2.91 respectively in the conjunctiva of the naive group. Histamine increased the eosinophil count to 46.00±2.57 and neutrophils to 31.47±2.33. Post-induction treatment reduced eosinophils to 35.50±1.66 and neutrophils to 21.87±1.97, while pre-induction treatment significantly (P<0.01) decreased eosinophils to 26.00±2.92 and neutrophils to 14.53±2.31.

Conclusions : Topical administration of the NK1R antagonist effectively reduces allergy-induced ocular redness by decreasing SP release in the tear fluid and conjunctival leukocyte infiltration.

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