Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Mol Brain. 2024 Nov 22;17(1):84. doi: 10.1186/s13041-024-01160-z.
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.
神经炎症是青光眼病理的一个重要贡献者。针对该过程中的关键介质是减缓疾病进展的现实选择。半乳糖凝集素-3 是一种 β-半乳糖苷结合凝集素，与全身性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升高的半乳糖凝集素-3，并且通过玻璃体内注射 TD139（一种半乳糖凝集素-3 小分子抑制剂）抑制半乳糖凝集素-3 具有神经保护作用。我们询问这种神经保护作用是否可以转化为另一种动物模型和物种。在诱导眼高压（眼压峰值）后 3 天，将 TD139 玻璃体内注射到青光眼大鼠眼高压模型中。定量检测视网膜神经节细胞存活和神经胶质形态标志物。TD139 注射可防止视网膜神经节细胞变性，但大体神经胶质标志物仍未受影响。这些数据证实，玻璃体内注射 TD139 在大鼠眼高压型青光眼模型中具有神经保护作用，同时表明抑制半乳糖凝集素-3 不足以改变大体炎症结局。
