A porcine commotio retinae model for preclinical evaluation of posttraumatic photoreceptor degeneration.

Abstract

Commotio retinae (CR) resulting from retinal trauma can lead to focal photoreceptor degeneration and permanent vision loss. Currently no therapies exist for CR-induced retinal degeneration, in part because of the lack of a large-animal model that replicates human injury pathology and allows testing of therapeutics. Severe CR is clinically characterized by subretinal fluid and focal photoreceptor outer nuclear layer thinning. To develop a porcine CR model, we developed a laser-guided projectile apparatus and optimized projectile delivery procedure using porcine cadaveric eyes embedded in a 3D-printed porcine skull. Scleral and corneal impacts resulted in retinal damage consistent with patient injury, but corneal impacts also led to cornea damage and opacification, which precluded follow-up imaging. In live porcine eyes, scleral impacts of 39.5 m/s induced transient blood-retinal barrier breakdown evidenced by subretinal fluid on optical coherence tomography (OCT), leakage observed on fluorescein and indocyanine green angiography, and transient photoreceptor outer segment disruption seen by OCT and multifocal electroretinography. Impacts above 39.5 m/s induced longer-lasting photoreceptor degeneration but only transient blood-retinal barrier breakdown. This porcine model, combined with clinically relevant imaging and diagnostic modalities, will be valuable for testing the safety and efficacy of therapies to restore vision after focal photoreceptor degeneration.