Rod Photoreceptor Neuroprotection in Dark-Reared Pde6brd10 Mice.
Rod Photoreceptor Neuroprotection in Dark-Reared Pde6brd10 Mice.
复制标题
DOI：
10.1167/iovs.61.13.14
复制
发表时间：
2020-11-02
影响因子：
4.4
通讯作者：
Roberts R
中科院分区：
文献类型：
--
作者：
Berkowitz BA;Podolsky RH;Childers KL;Roche SL;Cotter TG;Graffice E;Harp L;Sinan K;Berri AM;Schneider M;Qian H;Gao S;Roberts R
本研究的目的是检验抑制周期性光饲养Pde 6 brd 10小鼠视杆细胞死亡的抗氧化剂和/或抗炎药物在暗饲养Pde 6 brd 10小鼠中也有效的假设。在出生后（P）第23至24天未处理的暗养Pde 6 brd 10小鼠中，我们测量了外核层（ONL）厚度外界膜-视网膜色素上皮（ELM-RPE）的组织学和明暗厚度差异（光学相干断层扫描[OCT]），视网膜层氧化应激（QUEnch辅助[QUEST]磁共振成像[MRI]）;和小胶质细胞/巨噬细胞驱动的炎症（免疫组织学）。在黑暗饲养的P50 Pde 6 brd 10小鼠中，在给予正常食物或与亚甲蓝（MB）+炔诺孕酮（抗氧化剂、抗炎剂）混合的食物或分别给予MB或炔诺孕酮的食物的组中测量ONL厚度（OCT）。P24 Pde 6 brd 10小鼠在上级和下级视网膜中未显示与高cGMP水平一致的显著的暗光ELM-RPE反应。炔诺孕酮没有显著抑制Pde 6 brd 10小鼠的氧化应激，该氧化应激仅在P23时雄性的上级中央外视网膜中发现。在雄性和雌性P23 Pde 6 brd 10小鼠中观察到明显的视杆变性伴小胶质细胞/巨噬细胞活化，但仅在远周上级视网膜中观察到。在给予5 mg/kg/天MB +炔诺孕酮饲料的雌性P50 Pde 6 brd 10小鼠中测量到显著的视杆保护;在MB饲料或炔诺孕酮单独饲料以及类似处理的雄性小鼠中均未观察到显著获益。在黑暗饲养的Pde 6 brd 10小鼠的早期视杆变性中，在中央视网膜中几乎没有发现PDE 6 B突变、氧化应激和视杆死亡的生物标志物之间的空间关联的证据; P50时的神经保护仅限于以性别特异性方式进行的抗氧化剂/抗炎治疗的组合。
The purpose of this study was to test the hypothesis that anti-oxidant and / or anti-inflammation drugs that suppress rod death in cyclic light-reared Pde6brd10 mice are also effective in dark-reared Pde6brd10 mice. In untreated dark-reared Pde6brd10 mice at post-natal (P) days 23 to 24, we measured the outer nuclear layer (ONL) thickness (histology) and dark-light thickness difference in external limiting membrane-retinal pigment epithelium (ELM-RPE) (optical coherence tomography [OCT]), retina layer oxidative stress (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]); and microglia/macrophage-driven inflammation (immunohistology). In dark-reared P50 Pde6brd10 mice, ONL thickness was measured (OCT) in groups given normal chow or chow admixed with methylene blue (MB) + Norgestrel (anti-oxidant, anti-inflammatory), or MB or Norgestrel separately. P24 Pde6brd10 mice showed no significant dark-light ELM-RPE response in superior and inferior retina consistent with high cGMP levels. Norgestrel did not significantly suppress the oxidative stress of Pde6brd10 mice that is only found in superior central outer retina of males at P23. Overt rod degeneration with microglia/macrophage activation was observed but only in the far peripheral superior retina in male and female P23 Pde6brd10 mice. Significant rod protection was measured in female P50 Pde6brd10 mice given 5 mg/kg/day MB + Norgestrel diet; no significant benefit was seen with MB chow or Norgestrel chow alone, nor in similarly treated male mice. In early rod degeneration in dark-reared Pde6brd10 mice, little evidence is found in central retina for spatial associations among biomarkers of the PDE6B mutation, oxidative stress, and rod death; neuroprotection at P50 was limited to a combination of anti-oxidant/anti-inflammation treatment in a sex-specific manner.
登录
查看更多内容
影响因子：
4.4
作者：
Berkowitz BA;Podolsky RH;Lenning J;Khetarpal N;Tran C;Wu JY;Berri AM;Dernay K;Shafie-Khorassani F;Roberts R
通讯作者：
Roberts R
影响因子：
4.4
作者：
Allocca, Mariacarmela;Manfredi, Anna;Auricchio, Alberto
通讯作者：
Auricchio, Alberto
影响因子：
--
作者：
Cronin, Therese;Lyubarsky, Arkady;Bennett, Jean
通讯作者：
Bennett, Jean
影响因子：
4.4
作者：
Berkowitz, Bruce A.;Grady, Edmund Michael;Roberts, Robin
通讯作者：
Roberts, Robin
DOI：
10.1073/pnas.0605790103
发表时间：
2006-11-14
影响因子：
11.1
作者：
Cheng, Haiying;Nair, Govind;Duong, Timothy Q.
通讯作者：
Duong, Timothy Q.