A Tropomycin-Related Kinase B Receptor Activator for the Management of Ocular Blast-Induced Vision Loss
| Autor: | Curran Sidhu, Frank E. McDonald, Noah A. Setterholm, Eldon E. Geisert, Polina Lyuboslavsky, Micah A Chrenek, Jeffrey H Boatright, Susov Dhakal, Jana T Sellers, P. Michael Iuvone, Li He |
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| Rok vydání: | 2021 |
| Předmět: |
genetic structures
Blindness Neuroprotection Retina Time-to-Treatment Mice Eye Injuries Blast Injuries Blood-Retinal Barrier Animals Receptor trkB Medicine Receptor Kinase Activator (genetics) business.industry Brain-Derived Neurotrophic Factor fungi Traumatic optic neuropathy food and beverages Original Articles eye diseases Mice Inbred C57BL Neuroprotective Agents Treatment Outcome Blood-Brain Barrier Optic Nerve Injuries Cancer research Neurology (clinical) business |
| Zdroj: | J Neurotrauma |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | Pressure waves from explosions or other traumatic events can damage the neurons of the eye and visual centers of the brain, leading to functional loss of vision. There are currently few treatments for such injuries that can be deployed rapidly to mitigate damage. Brain-derived neurotrophic factor (BDNF) and activation of its receptor tropomycin-related kinase B (TrkB) have neuroprotective effects in a number of degeneration models. Small molecule activators of TrkB, such as N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC), cross the blood–brain and blood-retina barriers after systemic administration. We characterize the effects of blast-induced ocular trauma on retinal and visual function. We show that systemic administration of HIOC, a potent small molecule activator of the BDNF/TrkB receptor, preserves visual function in mice exposed to ocular blast injury. The HIOC treatment for one week preserves visual function for at least four months. The HIOC treatment effectively protected vision when the initial dose was administered up to 3 h after blast, but not if the initial treatment was delayed for 24 h. We provide evidence that the therapeutic effect of HIOC is mediated by activation of BDNF/TrkB receptors. The results indicate that HIOC may be useful for managing ocular blast injury and other forms of traumatic optic neuropathy. |
| Databáze: | OpenAIRE |
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