Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Exp Eye Res. 2020 Apr;193:107961. doi: 10.1016/j.exer.2020.107961. Epub 2020 Feb 8.
Glaucoma is a progressive neurodegenerative process affecting the retinal ganglion cells (RGCs) and the optic nerve. Oxidative stress has been implicated in glaucoma pathogenesis, and iron is a potent generator of oxidative stress. The oral iron chelator deferiprone (DFP) is protective against retinal degenerations associated with oxidative stress. To test whether DFP could be protective in glaucoma, we used microbead injections to induce elevated intraocular pressure (IOP) in a cohort of 3-month old C57BL/6J mice. One eye of each animal was injected with magnetic microbeads resulting in ocular hypertension for >7 weeks while the fellow eye was injected with saline and served as a normotensive internal control. While half of the cohort received oral DFP (1 mg/ml in the drinking water), the other half did not and served as controls. After 8 weeks, Brn3a immunolabeling of flat-mounted retinas was used for manual RGC quantification. Axon counts were obtained from thin sections of optic nerves using the AxonJ plugin for ImageJ. DFP administration was protective against RGC and optic nerve loss in the setting of elevated IOP. These results suggest that iron chelation by DFP may provide glaucoma neuroprotection.
青光眼是一种影响视网膜神经节细胞（RGC）和视神经的进行性神经退行性疾病。氧化应激与青光眼的发病机制有关，而铁是产生氧化应激的有力因素。口服铁螯合剂地拉罗司（DFP）可预防与氧化应激相关的视网膜变性。为了测试 DFP 是否对青光眼具有保护作用，我们使用微珠注射法在一组 3 个月大的 C57BL/6J 小鼠中诱导眼内压（IOP）升高。每只动物的一只眼注射磁性微珠，导致眼高压超过 7 周，而另一只眼注射生理盐水作为正常眼压的内部对照。一半的动物接受了口服 DFP（饮用水中 1mg/ml）治疗，另一半则未接受治疗作为对照。8 周后，使用 Brn3a 免疫标记对视网膜进行 flat-mounted 以进行手动 RGC 定量。使用 ImageJ 的 AxonJ 插件从视神经的薄切片中获得轴突计数。DFP 治疗可预防升高的 IOP 下的 RGC 和视神经丢失。这些结果表明，DFP 通过螯合铁可能提供青光眼神经保护作用。
