Specialized Pro-Resolving Lipid Mediators, Maresin 1 (MaR1) and Neuroprotectin D1 (NPD1) Reduce Gliosis in Retina and Optic Nerve after Blast Exposure

Abstract

Purpose : To investigate specialized pro-resolving lipid mediator (SPMs) as neuroprotective interventions to ameliorate neuroinflammation caused by blast exposure. We hypothesized that early administration of the SPMs, NPD1 or MaR1, will mitigate neuroinflammation, preserving retinal and optic nerve tissues after blast exposure in a blast-induced eye injury model.

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. 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. Rats were euthanized at 9, 23, and 33 days after blast exposure. The retina and optic nerve tissue were subjected to immunohistochemistry and Western Blots analyses for glial fibrillary acidic protein (GFAP) and for ionized calcium-binding adaptor 1 (Iba1) as indicators of gliosis. Tissues were evaluated for relative levels of positive signals compared to the unexposed controls.

Results : An increase in GFAP-immunostaining was detected throughout the Müller cell processes traversing the inner plexiform layer and in retinal ganglion cells of vehicle blast-exposed rats compared to controls. Immunolabeling of Iba-1 showed an increase in microglia reactivity in the retinas and optic nerve at 9, 23, and 33 days post blast of vehicle-treated blast rats compared to controls. Western Blot analysis showed a ~1.5-fold increase in GFAP protein levels in optic nerve homogenates from vehicle-treated blast exposed rats as compared to the control group. MaR1 and NPD1 treatment reduced GFAP upregulation and mitigated microglial reactivity in the retina and optic nerve up to 33 days after blast injury.

Conclusions : Blast wave exposure resulting in retinal damage, manifested by increased expression of proteins involved in gliosis, was reduced by either MaR-1 and/or NPD1 intervention. Thus the treatments of MaR1 or NPD1 suggest an effective strategy to reduce or halt retina and optic nerve glia cell activation due to blast wave exposures.

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