Arginine–Threonine–Arginine (RTR) Tetramer Reduces the Severity and Incidence of Ulcers in the Alkali–Injured Rabbit Cornea

Abstract

Abstract: : Purpose: To determine if topical application of two isomers of Arginine–Threonine–Arginine tetramer (L–RTR vs. D–RTR), constructed by Molecular Recognition Theory, can reduce the incidence and severity of corneal ulceration after alkali–injury. This approach is driven by known steric binding of RTR to N–acetyl Proline–Glycine–Proline (PGP), the initial neutrophil chemoattractant released from alkali–injured cornea. Methods:The corneas of 48 rabbits were exposed to 1N NaOH for 35 seconds. Sixteen animals were randomly assigned to each of three groups (1) 1.5 mM L–RTR tetramer (2) 0.8 mM D–RTR tetramer or (3) phosphate buffered saline (PBS) control. One drop was administered topically every hour, (14 times per day) for 36 days. Results: The severity of ulceration in the PBS control group was statistically greater than in both RTR groups from the 21st day of the experiment to the end. The incidence of ulcers was statistically decreased in the L–RTR group beginning on day 22 and continuing to the end. (L–RTR 19%, D–RTR 37%, PBS 56%) Healing also occurred in the D–RTR group but the incidence was not statistically different from L–RTR or PBS control. Conclusions: We believe that RTR binding with the degradation products of alkali–injury reduced the initial influx of neutrophils into the cornea. Reduction in the neutrophil stromal load diminishes the severity and incidence of ulceration, and allows the reparative process to proceed as evidenced by the healing of ulcers in the RTR tetramer groups.

Keywords: cornea: basic science • inflammation • wound healing