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Effect of MMP-9 gene knockout on retinal vascular form and function.
Physiological Genomics ( IF 2.5 ) Pub Date : 2019-11-11 , DOI: 10.1152/physiolgenomics.00041.2019
Akash K George 1, 2 , Rubens P Homme 1, 2 , Avisek Majumder 3 , Suresh C Tyagi 2 , Mahavir Singh 1, 2
Affiliation  

Retinal degeneration from inherited gene mutation(s) is a common cause of blindness because of structural and functional alterations in photoreceptors. Accordingly, various approaches are being tested to ameliorate or even cure neuroretinal blinding conditions in susceptible patients by employing neuroprotective agents, gene therapeutics, optogenetics, regenerative therapies, and retinal prostheses. The FVB/NJ mouse strain inherently has a common Pde6b rd1 homozygous allele that renders its progeny blind by the time pups reach weaning age. To study the role matrix metalloproteinase-9 (MMP-9) in retinal structure and function, we examined a global MMP-9 knockout (KO) mouse model that has been engineered on the same FVB/NJ background to test the hypothesis whether lack of MMP-9 activity diminishes neuroretinal degenerative changes and thus helps improve the vision. We compared side-by-side various aspects of the ocular physiology in the wild-type (WT) C57BL/6J, FVB/NJ, and MMP-9 KO strains of mice. The results suggest that MMP-9 KO mice display subdued changes in their retinae as reflected by both structural and functional enhancement in the overall ocular neurophysiological parameters. Altogether, the findings appear to have clinical relevance for targeting conditions wherein MMPs and their overactivities are suspected to play dominant pathophysiological roles in advancing neurodegenerative retinal diseases.

中文翻译:

MMP-9基因敲除对视网膜血管形态和功能的影响。

由于光感受器的结构和功能改变,遗传基因突变引起的视网膜变性是失明的常见原因。因此,通过使用神经保护剂,基因​​治疗剂,光遗传学,再生疗法和视网膜假体,正在测试各种方法来改善或什至治愈易感患者的神经视网膜盲状态。FVB / NJ小鼠品系固有地具有一个常见的Pde6b rd1纯合等位基因,当幼犬达到断奶年龄时,其后代就变得盲目。为了研究基质金属蛋白酶9(MMP-9)在视网膜结构和功能中的作用,我们检查了已在相同FVB / NJ背景上设计的全局MMP-9敲除(KO)小鼠模型,以检验是否缺乏MMP-9活性会减少神经视网膜退行性改变从而有助于改善视力的假说。我们比较了小鼠野生型(WT)C57BL / 6J,FVB / NJ和MMP-9 KO菌株的眼生理学各个方面。结果表明,MMP-9 KO小鼠的视网膜表现出柔和的变化,这在整体眼神经生理参数的结构和功能上均得到了增强。总之,这些发现似乎与靶向条件有关,其中MMPs及其过度活性被怀疑在推进神经变性视网膜疾病中起主要病理生理作用。我们比较了小鼠野生型(WT)C57BL / 6J,FVB / NJ和MMP-9 KO菌株的眼生理学各个方面。结果表明,MMP-9 KO小鼠的视网膜表现出柔和的变化,这在整体眼神经生理参数的结构和功能上均得到了增强。总之,这些发现似乎与靶向条件有关,其中MMPs及其过度活性被怀疑在神经退行性视网膜疾病的发展中起主要病理生理作用。我们比较了小鼠野生型(WT)C57BL / 6J,FVB / NJ和MMP-9 KO菌株的眼生理学各个方面。结果表明,MMP-9 KO小鼠的视网膜表现出柔和的变化,这在整体眼神经生理参数的结构和功能上均得到了增强。总之,这些发现似乎与靶向条件有关,其中MMPs及其过度活性被怀疑在神经退行性视网膜疾病的发展中起主要病理生理作用。
更新日期:2019-11-01
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