A Novel Animal Model of Optic Nerve Transection with Preservation of the Retinal Viability
Vahe Fahradyan, MD, Eliana Duraes, MD, PhD, Cagri Cakmakoglu, MD, Maria Madajka, PhD, Grzegorz Kwiecien, MD, Michaela Edmond, BS, Chris Link, BS, Addison Barnett, BS, Bell Allen Brent, BS, Neal Peachey, PhD, Antonio Rampazzo, MD, PhD, Alex Yuan, MD, PhD, Bahar Bassiri Gharb, MD, PhD, Frank Papay, MD.
Cleveland Clinic, Cleveland, OH, USA.
PURPOSE: Poor optic nerve regeneration still remains one of the major challenges preventing successful eye transplantation. The purpose of this study was to establish an optic nerve transection model that would allow evaluation of the axonal regeneration of retinal ganglion cells.
METHODS: Lewis rats were dissected, optic nerves were exposed and transected to create a clean-cut injury. An incision along the superior orbital rim and extending to the lateral temporal area with partial excision of temporalis muscle provided adequate exposure of the optic nerve. The levator palpebrae superioris and superior rectus muscles were transected, the Harderian and lacrimal glands were retracted and preserved. A superior-temporal minimal transverse incision was made on dura mater that provided enough space for optic nerve transection and allowed to retain the integrity of the ophthalmic artery and posterior ciliary artery, which is localized along the posterior nasal side of the optic nerve. Spectral domain optical coherence tomography (SD-OCT), electroretinography (ERG) and confocal scanning laser ophthalmoscopy (cSLO) were used to evaluate morphology, electrical activity and vascular integrity of the retina.
RESULTS: SD-OCT detected progressive atrophy of the retinal nerve fiber layer (RNFL) over the post-operative 12 weeks follow up period. Starting from week 4 there was a noticeable (19.1%) reduction of the RNFL, however, it was not statistically significant (p>0.05) compared to the control side. The difference became statistically significant (p<0.05) at week 6 and by post-operative 12-week RNFL on operated side was reduced by 54.3%. However, the total retinal thickness on the operated side was reduced only by 21.8% (p<0.05). SLO fluorescein and indocyanine green angiography revealed preservation of retinal and choroidal vasculature. Positive peaks were detected on the ERGs of operated eyes in response to flashlight stimulation. However, the amplitudes of the waves were decreased in operated eyes compared to control side.
CONCLUSION: We developed optic nerve complete transection model that maintains the integrity of the ophthalmic artery and retinal perfusion, which is essential for the preservation of the viability of the retina and evaluation of the optic nerve regeneration.
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