Loo Jing Hong, Wang Zhaoran, Chong Rachel S
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Duke-NUS Medical School, Singapore, Singapore.
Front Med (Lausanne). 2023 Jan 24;10:1087123. doi: 10.3389/fmed.2023.1087123. eCollection 2023.
Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found in most cell types. Cav-1 has been found to contribute significantly to ocular function, with mutations of Cav-1 being associated with a genetic risk of glaucoma development. Raised intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. Cav-1 may be involved in both IOP-dependent and independent mechanisms involving vascular dysregulation. Systemic vascular diseases including hypertension, diabetes and hyperlipidaemia, have been shown to be associated with glaucoma development. Cav-1 is closely interlinked with endothelial nitric oxide synthase pathways that mediate vascular function and prevent cardiovascular diseases. Endothelial nitric oxide synthase and endothelin-1 are key vasoactive molecules expressed in retinal blood vessels that function to autoregulate ocular blood flow (OBF). Disruptions in the homeostasis of OBF have led to a growing concept of impaired neurovascular coupling in glaucoma. The imbalance between perfusion and neuronal stimulation arising from Cav-1 depletion may result in relative ischemia of the optic nerve head and glaucomatous injury. OBF is also governed by circadian variation in IOP and systemic blood pressure (BP). Cav-1 has been shown to influence central BP variability and other circadian rhythms such as the diurnal phagolysosomal digestion of photoreceptor fragments and toxic substrates to maintain ocular health. Overall, the vast implications of Cav-1 on various ocular mechanisms leading to glaucoma suggest a potential for new therapeutics to enhance Cav-1 expression, which has seen success in other neurodegenerative diseases.
小窝蛋白-1（Cav-1）是一种存在于大多数细胞类型中的整合性支架膜蛋白。已发现Cav-1对眼功能有显著贡献，Cav-1的突变与青光眼发生的遗传风险相关。眼压升高（IOP）是青光眼的一个主要可改变风险因素。Cav-1可能参与涉及血管调节异常的眼压依赖性和非依赖性机制。包括高血压、糖尿病和高脂血症在内的全身性血管疾病已被证明与青光眼的发生有关。Cav-1与介导血管功能和预防心血管疾病的内皮型一氧化氮合酶途径密切相关。内皮型一氧化氮合酶和内皮素-1是视网膜血管中表达的关键血管活性分子，其功能是自动调节眼血流量（OBF）。OBF稳态的破坏导致了青光眼神经血管耦合受损这一概念的不断发展。Cav-1缺失引起的灌注与神经元刺激之间的失衡可能导致视神经乳头相对缺血和青光眼性损伤。OBF也受眼压和全身血压（BP）昼夜变化的影响。已证明Cav-1会影响中心血压变异性和其他昼夜节律，如光感受器碎片和有毒底物的昼夜吞噬溶酶体消化，以维持眼部健康。总体而言，Cav-1对导致青光眼的各种眼部机制具有广泛影响，这表明增强Cav-1表达的新疗法具有潜力，这已在其他神经退行性疾病中取得成功。
