青光眼是世界范围内第三大失明原因,其主要特征在于眼内压(IOP)升高。常见的风险因素，如年龄，近视,眼外伤,和高血压都会增加IOP升高的风险。长时间的高眼压不仅会引起头痛等生理不适，但也直接损害视网膜细胞，导致视网膜缺血，氧化失衡，和视网膜中活性氧（ROS）的积累。这种氧化应激导致蛋白质和不饱和脂质的氧化，导致过氧化物形成和加剧视网膜损伤。虽然目前的临床治疗主要针对通过药物或手术降低IOP，目前没有有效的方法来减轻与青光眼相关的视网膜细胞损伤。为了解决这个差距，我们开发了一种新型纳米乳剂,用于共同递送拉坦前列素和α-生育酚(后来称为LA@VNE),通过局部给药延长眼部滞留并增强视网膜通透性.通过封装拉坦前列素，一种降低眼压的药物,和α-生育酚，一种强效的抗氧化剂,我们有效地减少了ROS的积累（体外>1.5倍，体内>2.5倍），视网膜神经节细胞（RGC）凋亡（>9倍），和炎性细胞浸润(>1.6倍)。我们的方法显示出强的生物相容性和临床翻译的显著潜力，为青光眼的治疗提供了一个有前途的平台。
Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.
