Zhang Chi, Simón Marina, Harder Jeffrey M, Lim Haeyn, Montgomery Christa, Wang Qing, John Simon W M
Department of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
Sci Rep. 2025 May 15;15(1):16852. doi: 10.1038/s41598-025-00638-7.
Glaucoma is a leading cause of irreversible blindness worldwide. Toll-like receptor 4 (TLR4) is a pattern-recognition transmembrane receptor that induces neuroinflammatory processes in response to injury. Tlr4 is highly expressed in ocular tissues and is known to modulate inflammatory processes in both anterior and posterior segment tissues. TLR4 activation can lead to mitochondrial dysfunction and metabolic deficits in inflammatory disorders. Due to its effects on inflammation and metabolism, TLR4 is a candidate to participate in glaucoma pathogenesis. It has been suggested as a therapeutic target based on studies using acute models, such as experimentally raising IOP to ischemia-inducing levels. Nevertheless, its role in chronic glaucoma needs further evaluation. In the current study, we investigated the role of TLR4 in an inherited mouse model of chronic glaucoma, DBA/2J. To do this, we analyzed the effect of Tlr4 knockout (Tlr4) on glaucoma in DBA/2J mice. Our studies found no significant differences in intraocular pressure, iris disease, or glaucomatous progression in Tlr4 compared to Tlr4 DBA/2J mice. Our data do not support a role for TLR4 as a treatment target in chronic glaucoma.
青光眼是全球不可逆性失明的主要原因。Toll样受体4（TLR4）是一种模式识别跨膜受体，可响应损伤诱导神经炎症过程。Tlr4在眼组织中高度表达，已知可调节眼前段和后段组织中的炎症过程。TLR4激活可导致炎症性疾病中的线粒体功能障碍和代谢缺陷。由于其对炎症和代谢的影响，TLR4是参与青光眼发病机制的一个候选因素。基于使用急性模型的研究，如通过实验将眼压升高到诱导缺血的水平，它已被建议作为一个治疗靶点。然而，其在慢性青光眼中的作用需要进一步评估。在当前的研究中，我们研究了TLR4在遗传性慢性青光眼小鼠模型DBA/2J中的作用。为此，我们分析了Tlr4基因敲除（Tlr4-/-）对DBA/2J小鼠青光眼的影响。我们的研究发现，与Tlr4+ DBA/2J小鼠相比，Tlr4-/-小鼠在眼压、虹膜疾病或青光眼进展方面没有显著差异。我们的数据不支持TLR4作为慢性青光眼治疗靶点的作用。
