Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma

Abstract Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervou...

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Main Authors: Anne Rombaut, Rune Brautaset, Pete A. Williams, James R. Tribble
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-024-01160-z
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author Anne Rombaut
Rune Brautaset
Pete A. Williams
James R. Tribble
author_facet Anne Rombaut
Rune Brautaset
Pete A. Williams
James R. Tribble
author_sort Anne Rombaut
collection DOAJ
description Abstract Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervous system diseases. Elevated Galectin-3 has recently been detected in multiple animal models of glaucoma and inhibiting Galectin-3 using an intravitreal injection of TD139 (a Galectin-3 small molecule inhibitor) is neuroprotective. We queried whether this neuroprotective effect was translatable to another animal model and species. TD139 was intravitreally injected, in a rat ocular hypertensive model of glaucoma, 3 days after the induction of ocular hypertension (at peak intraocular pressure). Retinal ganglion cell survival and glial morphological markers were quantified. The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome.
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spelling doaj-art-4e5b23d2a1a04099a223a787e8b2bf3a2025-08-20T02:22:16ZengBMCMolecular Brain1756-66062024-11-011711410.1186/s13041-024-01160-zIntravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucomaAnne Rombaut0Rune Brautaset1Pete A. Williams2James R. Tribble3Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetAbstract Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervous system diseases. Elevated Galectin-3 has recently been detected in multiple animal models of glaucoma and inhibiting Galectin-3 using an intravitreal injection of TD139 (a Galectin-3 small molecule inhibitor) is neuroprotective. We queried whether this neuroprotective effect was translatable to another animal model and species. TD139 was intravitreally injected, in a rat ocular hypertensive model of glaucoma, 3 days after the induction of ocular hypertension (at peak intraocular pressure). Retinal ganglion cell survival and glial morphological markers were quantified. The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome.https://doi.org/10.1186/s13041-024-01160-zGalectin-3TD139NeurodegenerationNeuroinflammationNeuroprotectionRetina
spellingShingle Anne Rombaut
Rune Brautaset
Pete A. Williams
James R. Tribble
Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
Molecular Brain
Galectin-3
TD139
Neurodegeneration
Neuroinflammation
Neuroprotection
Retina
title Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
title_full Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
title_fullStr Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
title_full_unstemmed Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
title_short Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
title_sort intravitreal injection of the galectin 3 inhibitor td139 provides neuroprotection in a rat model of ocular hypertensive glaucoma
topic Galectin-3
TD139
Neurodegeneration
Neuroinflammation
Neuroprotection
Retina
url https://doi.org/10.1186/s13041-024-01160-z
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