Hadziahmetovic Majda, Pajic Miroslav, Grieco Steven, Song Ying, Song Delu, Li Yafeng, Cwanger Alyssa, Iacovelli Jared, Chu Sally, Ying Gui-Shuang, Connelly John, Spino Michael, Dunaief Joshua L
F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA.
Transl Vis Sci Technol. 2012 Oct 25;1(3):2. doi: 10.1167/tvst.1.3.2. eCollection 2012.
To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO)-induced retinal degeneration and on the hereditary retinal degeneration caused by the mutation.
Retinas from NaIO-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, mice treated with or without DFP were analyzed by histology to assess possible protection.
In NaIO-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress-related gene heme oxygenase-1 and the complement gene . DFP treatment partially protected against NaIO-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin () and retinal pigment epithelium-specific 65 kDa protein (), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in mice.
The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation.
These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted.
研究铁螯合剂去铁酮（DFP）对碘酸钠（NaIO）诱导的视网膜变性以及对由该突变引起的遗传性视网膜变性的影响。
对经NaIO处理的C57BL/6J小鼠的视网膜，无论是否联合DFP处理，进行组织学、免疫荧光和定量PCR分析，以研究DFP对视网膜变性的影响。为便于对光感受器进行定量分析，我们开发了MATLAB的一项新功能，以半自动方式执行此任务。此外，对经或未经DFP处理的小鼠进行组织学分析，以评估可能的保护作用。
在经NaIO处理的小鼠中，DFP可预防视网膜变性，并显著降低氧化应激相关基因血红素加氧酶-1和补体基因的表达。DFP处理部分预防了NaIO诱导的视循环基因视紫红质（）和视网膜色素上皮特异性65 kDa蛋白（）编码的mRNA水平降低，这与形态学数据一致，分别表明光感受器和视网膜色素上皮得以保留。DFP处理还保护了小鼠中的光感受器。
口服铁螯合剂DFP对通过不同方式诱导的视网膜变性具有显著的保护作用。这表明即使主要病因似乎并非铁调节异常，铁螯合也可能作为视网膜变性的一种治疗方法。
这些数据提供了原理证明，即口服铁螯合剂DFP可保护视网膜免受多种损伤。有必要在一系列剂量下对DFP在其他动物视网膜变性模型中进行进一步测试。
