BDNF and cAMP are neuroprotective in a porcine model of traumatic optic neuropathy

Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this o...

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Bibliographic Details
Published in:	JCI insight Vol. 9; no. 3
Main Authors:	Heng, Kathleen, Young, Brent K, Li, BaoXiang, Nies, Ashley D, Xia, Xin, Wen, Runxia R, Dalal, Roopa, Bramblett, Gregory T, Holt, Andrew W, Cleland, Jeffery M, Harris, Jason N, Wu, Albert Y, Goldberg, Jeffrey L
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 08-02-2024
Subjects:	Animals Axons - metabolism Brain-Derived Neurotrophic Factor - metabolism Nerve Regeneration Neuroprotection Optic Nerve Injuries - drug therapy Swine Swine, Miniature - metabolism Vision Disorders Retinopathy Ophthalmology
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Summary:	Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large-animal models are a major obstacle to advancing treatments toward clinical therapeutics. To address this issue, we refined a surgical model of TON in Yucatan minipigs. First, we validated the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we developed and optimized a delivery method and nontoxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cAMP. Finally, we showed that intravitreal injection of BDNF and cAMP rescued visual function and protected against retinal ganglion cell death and optic nerve axon degeneration. Together these data in a preclinical large-animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: KH and BKY contributed equally to this work and are co–first authors.
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.172935