Specialized Pro-Resolving Lipid Mediators, Maresin 1 (MaR1) and Neuroprotectin D1 (NPD1), Preserve Retinal Rod Function After Ocular Blast Trauma

Abstract

Purpose : To investigate specialized pro-resolving lipid mediator (SPMs) as neuroprotective interventions to ameliorate neuroinflammation, mitigate tissue damage, and preserve visual function after blast exposure. We hypothesized that early administration of the SPMs, NPD1 or MaR1, will preserve visual function in a blast-induced eye injury model by mitigating injurious processes.

Methods : A compressed-air driven shock tube was used to expose anesthetized adult male Long-Evans rats to shock waves simulating an open-field blast exposure. Blast waves of peak overpressure of 133 ± 4 kPa and a positive phase duration of 3.34 ± 0.05 ms were used. The overpressure specific impulse was 163.5 ± 10.4 kPa-ms. Anesthetized rats were exposed to a blast wave. Approximately 30 minutes after blast exposure, rats were treated with either 1.0 µg/kg MaR-1, 0.1 µg/kg NPD1 or vehicle (0.9% saline) delivered via tail vein injection and treated daily thereafter until day 7. Unexposed rats were included as controls. Visual function was assessed using a UTAS BigShot workstation (LKC Technologies) at pre-blast and 8-, 22-, and 32-days post-blast timepoints. This initial analysis is based on the scotopic ERG response, using the Vmax and Km parameters obtained by fitting the Naka-Rushton equation to the scotopic V-LogI curve. Pre- and post-blast statistical analysis was done with ANOVA and Bonferroni multiple comparisons.

Results : The Naka-Rushton function yields an objective measure of Vmax (the maximum response of the ERG rod branch) and the Km (the stimulus intensity at half-maximal response). In rats exposed to the blast wave only, Vmax was reduced up to 25% by day 30 post-blast, compared to the pre-blast average (p≈0.003). In the blast-exposed and vehicle treated rats, Vmax was depressed up to 50% (p=0-.001) and Km was elevated (p=0.003), indicating reduced visual sensitivity. In the animals exposed to blast and treated with either MaR1 or NPD1, there was no significant change (p>.0.05) in the Vmax or Km, indicating maintained visual sensitivity.

Conclusions : Blast wave exposure resulting in retinal damage, manifested by loss of rod sensitivity, was mitigated by either MaR-1 and/or NPD1 intervention. Thus, the treatments of MaR1 or NPD1 suggest an effective strategy to preserve visual function due to retinal and optic nerve injuries following ocular blast trauma.

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