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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 6

Long-term evaluation of CR injury induced with a cadaveric scleral patch support.

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Long-term evaluation of CR injury induced with a cadaveric scleral patch...
(A) Color fundus image shows the area of impact with preretinal hemorrhage and the surrounding area of retinal whitening. (B) Late-phase (10 minutes) FA and ICGA show blocked fluorescence signal due to hemorrhage. Scale bars: 2 mm. (C) OCT showing subretinal fluid corresponding to the whitening area in A. Scale bar: 500 μm. (D–I) OCT images (D–F) and corresponding OCTA images (G–I) depicting the presence of ellipsoid zone and choriocapillaris, respectively, at baseline (D, arrowhead) and clear absence of ellipsoid zone at 30 days (E, arrowhead) and 60 days (F, arrowhead) after injury. Minimal changes are seen in choriocapillaris (compare G–I, arrowheads). Scale bars: 500 μm. (J) Median grayscale values intensity graph of OCTA signal intensity up to 60 days after CR injury. Results were analyzed using 1-way ANOVA. (K) Graph showing ONL thickness at baseline and 15, 30, and 60 days after projectile impact at 39.5 m/s on eyes with no scleral patch versus with scleral patch impacts. Data are presented as a percentage of average thickness of the same location at baseline. ANOVA (Friedman test compared with baseline) was used for statistical analysis. *P < 0.05, **P < 0.01. (L–N) mfERG heatmaps at baseline (L) and 30 days (M) and 60 days (N) after CR injury depicting changes in mfERG sensitivity throughout the evaluation time. Visual streak is highlighted by dashed ovals. Four eyes were used for this evaluation.

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