在眼压过高型青光眼大鼠模型中,玻璃体内注射 Galectin-3 抑制剂 TD139 可提供神经保护。

IF 3.3 3区 医学 Q2 NEUROSCIENCES Molecular Brain Pub Date : 2024-11-22 DOI:10.1186/s13041-024-01160-z
Anne Rombaut, Rune Brautaset, Pete A Williams, James R Tribble
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引用次数: 0

摘要

神经炎症是青光眼病理的一个重要因素。以这一过程中的关键介质为靶点是减缓疾病进展的现实选择。Galectin-3是一种β-半乳糖苷结合凝集素,与全身和中枢神经系统疾病中的炎症有关。最近在多种青光眼动物模型中检测到 Galectin-3 升高,通过玻璃体内注射 TD139(一种 Galectin-3 小分子抑制剂)抑制 Galectin-3 可起到神经保护作用。我们询问这种神经保护作用是否可转化为另一种动物模型和物种。在大鼠眼压过高型青光眼模型中,在诱导眼压过高3天后(眼压达到峰值时)进行玻璃体内注射TD139。对视网膜神经节细胞存活率和神经胶质形态标记进行了量化。注射 TD139 阻止了视网膜神经节细胞的退化,但总的神经胶质标记不受影响。这些数据证实,在大鼠眼压过高型青光眼模型中,玻璃体内注射 TD139 具有神经保护作用,同时也表明 Galectin-3 的抑制作用不足以改变严重的炎症结果。
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Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma.

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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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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