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A porcine commotio retinae model for preclinical evaluation of posttraumatic photoreceptor degeneration
Juan Amaral, Irina Bunea, Arvydas Maminishkis, Maria M. Campos, Francesca Barone, Rohan Gupta, Mitra Farnoodian, Jonathan Newport, M. Joseph Phillips, Ruchi Sharma, David M. Gamm, Kapil Bharti, Richard J. Blanch
Juan Amaral, Irina Bunea, Arvydas Maminishkis, Maria M. Campos, Francesca Barone, Rohan Gupta, Mitra Farnoodian, Jonathan Newport, M. Joseph Phillips, Ruchi Sharma, David M. Gamm, Kapil Bharti, Richard J. Blanch
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Research Article Neuroscience Ophthalmology

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

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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.

Authors

Juan Amaral, Irina Bunea, Arvydas Maminishkis, Maria M. Campos, Francesca Barone, Rohan Gupta, Mitra Farnoodian, Jonathan Newport, M. Joseph Phillips, Ruchi Sharma, David M. Gamm, Kapil Bharti, Richard J. Blanch

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Figure 4

CR injury recovery in the long-term evaluation.

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CR injury recovery in the long-term evaluation.
(A–F) Color fundus (A an...
(A–F) Color fundus (A and D), late-phase (10 minutes) FA (B and E, left panels), ICGA (B and E, right panels), and OCT (C and F) of post-injury eyes on day 0 (A–C) and day 16 (D–F) of evaluation of the same eye. “1” marks the area of impact showing preretinal hemorrhage. Whitened area in color fundus images corresponds to subretinal fluid accumulation on day 0, which is resolved by day 16 (arrowheads in C and F). Scale bars: 2 mm in A, B, D, and E; 500 μm in C and F. (G–L) OCT (G–I) and mfERG (J–L) analysis shows recovery of ellipsoid zone (EZ) (compare arrowheads in G–I) and recovery of mfERG signal in the visual streak (dashed ovals, J–L) by day 30 in eyes injured with a projectile speed of 35.7 m/s. Scale bars: 50 μm. (M–R) Comparative analysis at 60 days after injury using OCT (M and P), OCT angiography (N and Q), and mfERG (O and R) of 2 eyes injured with a projectile speed of 39.5 m/s highlights variability in damage to the outer retina and to the ellipsoid zone (arrowheads in M and P) and to the choriocapillaris (arrowheads in N and Q), and the variable signal in the visual streak (VS; dashed ovals) (O and R). Scale bars: 1 mm in M and P, 500 μm in N and Q. Seven eyes were used for this evaluation.

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