PDF(Pubmed)
Abstract：
UNASSIGNED: Previous studies have reported Caspase-1 (Casp1) is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for Casp1 in disease progression has been identified. We performed electroretinogram (ERG) and standardized optical coherence tomography (OCT) in mice deficient in the Retinoschisin-1 (Rs1) and Casp1 and Caspase-11 (Casp11) genes (Rs1-KO;Casp1/11-/- ) to test the hypothesis that Casp1 may play a role in disease evolution and or severity of disease. Currently, no studies have ventured to investigate the longer-term effects of Casp1 on phenotypic severity and disease progression over time in XLRS, and specifically the effect on electroretinogram.
UNASSIGNED: Rs1-KO;Casp1/11-/- mice were generated by breeding Rs1-KO mice with Casp1/11-/- mice. OCT imaging was analyzed at 2-, 4-, and 15-16 months of age. Outer nuclear layer (ONL) thickness and adapted standardized cyst severity score were measured and averaged from 4 locations 500 μm from the optic nerve. Adapted standardized cyst severity score was 1: absent cysts, 2: <30 μm, 3: 30-49 μm, 4: 50-69 μm, 5: 70-99 μm, 6: >99 μm. Electroretinograms (ERG) were recorded in dark-adapted and light-adapted conditions at 2 and 4 months. Results obtained from Rs1-KO and Rs1-KO;Casp1/11-/- eyes were compared with age matched WT control eyes at 2 months.
UNASSIGNED: Intraretinal schisis was not observed on OCT in WT eyes, while schisis was apparent in most Rs1-KO and Rs1-KO;Casp1/11-/- eyes at 2 and 4 months of age. There was no difference in the cyst severity score from 2 to 4 months of age, or ONL thickness from 2 to 16 months of age between Rs1-KO and Rs1-KO;Casp1/11-/- eyes. ERG amplitudes were similarly reduced in Rs1-KO and Rs1-KO;Casp1/11-/- compared to WT controls at 2 months of age, and there was no difference between Rs1-KO and Rs1-KO;Casp1/11-/- eyes at 2 or 4 months of age, suggesting no impact on the electrical function of photoreceptors over time in the absence of Casp1.
UNASSIGNED: Although Casp1 has been reported to be significantly upregulated in Rs1-KO mice, our preliminary data suggest that removing Casp1/11 does not modulate photoreceptor electrical function or alter the trajectory of the retinal architecture over time.
UNASSIGNED: Rs1-KO;Casp1/11-/- mice were generated by breeding Rs1-KO mice with Casp1/11-/- mice. OCT imaging was analyzed at 2-, 4-, and 15-16 months of age. Outer nuclear layer (ONL) thickness and adapted standardized cyst severity score were measured and averaged from 4 locations 500 μm from the optic nerve. Adapted standardized cyst severity score was 1: absent cysts, 2: <30 μm, 3: 30-49 μm, 4: 50-69 μm, 5: 70-99 μm, 6: >99 μm. Electroretinograms (ERG) were recorded in dark-adapted and light-adapted conditions at 2 and 4 months. Results obtained from Rs1-KO and Rs1-KO;Casp1/11-/- eyes were compared with age matched WT control eyes at 2 months.
UNASSIGNED: Intraretinal schisis was not observed on OCT in WT eyes, while schisis was apparent in most Rs1-KO and Rs1-KO;Casp1/11-/- eyes at 2 and 4 months of age. There was no difference in the cyst severity score from 2 to 4 months of age, or ONL thickness from 2 to 16 months of age between Rs1-KO and Rs1-KO;Casp1/11-/- eyes. ERG amplitudes were similarly reduced in Rs1-KO and Rs1-KO;Casp1/11-/- compared to WT controls at 2 months of age, and there was no difference between Rs1-KO and Rs1-KO;Casp1/11-/- eyes at 2 or 4 months of age, suggesting no impact on the electrical function of photoreceptors over time in the absence of Casp1.
UNASSIGNED: Although Casp1 has been reported to be significantly upregulated in Rs1-KO mice, our preliminary data suggest that removing Casp1/11 does not modulate photoreceptor electrical function or alter the trajectory of the retinal architecture over time.
摘要：
■先前的研究报道，Caspase-1（Casp1）在幼年X连锁视网膜分裂（XLRS）的小鼠模型中上调，然而，尚未发现Casp1在疾病进展中的功能作用。我们对视网膜电图（ERG）和标准光学相干断层扫描（OCT）进行了视网膜电图（Rs1）和Casp1和Caspase-11（Casp11）基因（Rs1-KO；Casp1/11-/-）缺陷小鼠的视网膜电图（ERG）和标准化光学相干断层扫描（OCT），以检验Casp1可能在疾病演变和/或疾病严重程度中起作用的假设。目前,没有研究冒险调查Casp1对XLRS中表型严重程度和疾病随时间进展的长期影响，特别是对视网膜电图的影响。
■Rs1-KO;Casp1/11-/-小鼠通过用Casp1/11-/-小鼠饲养Rs1-KO小鼠来产生。OCT成像在2,4-,15-16个月大.测量外核层（ONL）厚度和适应的标准化囊肿严重程度评分，并从距视神经500μm的4个位置取平均值。适应的标准化囊肿严重程度评分为1：无囊肿，2:<30μm,3:30-49μm,4:50-69μm,5:70-99μm,6:>99μm。在2个月和4个月时，在暗适应和光照条件下记录视网膜电图（ERG）。从Rs1-KO和Rs1-KO获得的结果;在2个月时将Casp1/11-/-眼与年龄匹配的WT对照眼进行比较。
■在WT眼睛的OCT上未观察到视网膜内裂开，而分裂在大多数Rs1-KO和Rs1-KO中明显；Casp1/11-/-在2个月和4个月大时。2～4月龄囊肿严重程度评分无差异,或2至16月龄的ONL厚度在Rs1-KO和Rs1-KO之间;Casp1/11-/-眼。与2月龄的WT对照相比，Rs1-KO和Rs1-KO的ERG振幅也同样降低；Casp1/11-/-Rs1-KO和Rs1-KO之间没有差异；Casp1/11-/-2或4个月大的眼睛，表明在不存在Casp1的情况下，随着时间的推移对光感受器的电功能没有影响。
■尽管据报道Casp1在Rs1-KO小鼠中显著上调，我们的初步数据表明,随着时间的推移,去除Casp1/11不会调节光感受器的电功能或改变视网膜结构的轨迹.
■Rs1-KO;Casp1/11-/-小鼠通过用Casp1/11-/-小鼠饲养Rs1-KO小鼠来产生。OCT成像在2,4-,15-16个月大.测量外核层（ONL）厚度和适应的标准化囊肿严重程度评分，并从距视神经500μm的4个位置取平均值。适应的标准化囊肿严重程度评分为1：无囊肿，2:<30μm,3:30-49μm,4:50-69μm,5:70-99μm,6:>99μm。在2个月和4个月时，在暗适应和光照条件下记录视网膜电图（ERG）。从Rs1-KO和Rs1-KO获得的结果;在2个月时将Casp1/11-/-眼与年龄匹配的WT对照眼进行比较。
■在WT眼睛的OCT上未观察到视网膜内裂开，而分裂在大多数Rs1-KO和Rs1-KO中明显；Casp1/11-/-在2个月和4个月大时。2～4月龄囊肿严重程度评分无差异,或2至16月龄的ONL厚度在Rs1-KO和Rs1-KO之间;Casp1/11-/-眼。与2月龄的WT对照相比，Rs1-KO和Rs1-KO的ERG振幅也同样降低；Casp1/11-/-Rs1-KO和Rs1-KO之间没有差异；Casp1/11-/-2或4个月大的眼睛，表明在不存在Casp1的情况下，随着时间的推移对光感受器的电功能没有影响。
■尽管据报道Casp1在Rs1-KO小鼠中显著上调，我们的初步数据表明,随着时间的推移,去除Casp1/11不会调节光感受器的电功能或改变视网膜结构的轨迹.
