Rodrigo M J, Cardiel M J, Fraile J M, Mendez-Martinez S, Martinez-Rincon T, Subias M, Polo V, Ruberte J, Ramirez T, Vispe E, Luna C, Mayoral J A, Garcia-Martin E
Department of Ophthalmology, Miguel Servet University Hospital, Zaragoza, Spain.
Biomater Sci. 2020 Nov 21;8(22):6246-6260. doi: 10.1039/d0bm01013h. Epub 2020 Oct 5.
Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.
玻璃体内给药在眼科实践中被广泛应用，以维持神经视网膜附近的治疗药物水平，并且因为需要药物递送系统来避免重复注射和威胁视力的副作用。然而，目前尚无用于青光眼的玻璃体内治疗方法。溴莫尼定-LAPONITE®制剂的研发目的是通过单次玻璃体内注射长期治疗青光眼。在两个大鼠队列中通过诱导高眼压来诱发青光眼：[BRI-LAP]组和[非溴莫尼定]组，分别接受治疗和未接受治疗。用溴莫尼定-LAPONITE®治疗的眼睛在第8周时眼压水平较低（p < 0.001），通过暗视和明视负反应视网膜电图探索的功能性神经保护作用（p = 0.042），以及视网膜、视网膜神经纤维层和神经节细胞层的结构保护作用（p = 0.038），特别是在通过光学相干断层扫描探索的上下轴上，这一点在研究结束时（第24周）通过免疫组织化学（使用Brn3a抗体）获得的较高视网膜神经节细胞计数（p = 0.040）得到了证实。此外，在对侧眼中检测到了延迟的神经保护作用。在接受治疗的大鼠眼中检测到溴莫尼定长达6个月。溴莫尼定-LAPONITE®似乎是一种用于青光眼治疗的潜在长效玻璃体内给药药物。
