TrkB Receptor Agonist 7,8 Dihydroxyflavone is Protective Against the Inner Retinal Deficits Induced by Experimental Glaucoma

Gupta, Vivek, Chitranshi, Nitin, Gupta, Veer, You, Yuyi, Rajput, Rashi, Paulo, Joao A., Mirzaei, Mehdi, van den Buuse, Maarten, and Graham, Stuart L. (2022) TrkB Receptor Agonist 7,8 Dihydroxyflavone is Protective Against the Inner Retinal Deficits Induced by Experimental Glaucoma. Neuroscience, 490. pp. 36-48.

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Glaucoma is an age-related neurodegenerative disorder characterized by retinal ganglion cell (RGC) degeneration and excavation of the optic nerve head (ONH). It is associated with an increase in intraocular pressure (IOP) and progressive decline in the visual field. Reduction in the retrograde axonal transport of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) from the brain to the neuronal cell bodies in retina, has been suggested as one of the key mechanisms underlying selective degeneration of ganglion cells and optic nerve in glaucoma. Multiple studies have indicated that BDNF and its high affinity receptor Tropomyosin receptor kinase B (TrkB) play crucial roles in survival of RGCs and that upregulating BDNF/TrkB signalling using gene therapy can protect the ganglion cells against degeneration. This study corroborates previous findings and demonstrates that glaucoma is associated with downregulation of TrkB downstream signalling and enhanced levels of amyloid β (Aβ 1–42) accumulation in the retina. 7,8 dihydroxyflavone (7,8 DHF) is a TrkB agonist and regular administration of this compound imparted significant protection against loss of GCL density and preserved inner retinal function in experimental glaucoma models. 7,8 DHF treatment stimulated activation of TrkB intracellular signalling as well as ameliorated the increase in the levels of soluble Aβ (1–42) in the retinas of rats and mice exposed to high IOP. The protective effects of 7,8 DHF were also evident in BDNF+/− mice indicating that TrkB agonist mediated activation of TrkB signalling was not altered upon BDNF allelic impairment. These data support BDNF/TrkB axis as a promising therapeutic target in glaucoma and highlight that the detrimental effects of high IOP exposure can be compensated by the exogenous administration of a TrkB agonist.

Item ID: 74354
Item Type: Article (Research - C1)
ISSN: 1873-7544
Keywords: retina, glaucoma, 7 8 DHF, retinal ganglion cells, TrkB receptor, amyloid
Copyright Information: © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1136602, NHMRC 1139560
Date Deposited: 01 Jun 2022 08:39
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320907 Sensory systems @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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