UNASSIGNED: Conventional electroretinograms (ERGs) and dark-adapted 10-Hz flicker ERGs were recorded in control and Rs1 -/Y mice generated with CRISPR/Cas9. ON-pathway blocker 2-amino-4-phosphobutyric acid (APB) was injected intravitreally. Morphology was evaluated with histology and optical coherence tomography (OCT). Mice were treated with a CAI inhibitor brinzolamide eye drops (10 mg/ml) three times a day for 3 months. OCT and ERG findings at 1, 4, and 10 months were analyzed.
UNASSIGNED: Negative ERGs and retinal cavities were evident in Rs1 -/Y mice. Both a-wave and b-wave amplitudes decreased with age when compared with age-matched controls. The APB-isolated a-wave (a\') amplitudes of Rs1 -/Y mice were reduced in all age groups. In dark-adapted 10-Hz flicker ERG, the amplitude-intensity curve of Rs1 -/Y mice shifted down. The thickness of ONL and IS/OS decreased in Rs1 -/Y mice. CAI reduced the splitting retinal cavities but didn\'t affect the ERG.
UNASSIGNED: In addition to post receptoral impairments, photoreceptor cells underwent progressive dysfunction since early age in Rs1 -/Y mice. Long-term CAI treatment improved the shrinkage of the splitting retinal cavity, while no functional improvement was observed.
■在对照和用CRISPR/Cas9产生的Rs1-/Y小鼠中记录常规视网膜电图(ERG)和暗适应的10-Hz闪烁ERG。将ON途径阻断剂2-氨基-4-磷酸丁酸(APB)玻璃体内注射。用组织学和光学相干断层扫描(OCT)评估形态学。用CAI抑制剂布林佐胺滴眼剂(10mg/ml)治疗小鼠,每天三次,持续3个月。分析1、4和10个月时的OCT和ERG结果。
■在Rs1-/Y小鼠中出现明显的ERGs阴性和视网膜空洞。与年龄匹配的对照组相比,a波和b波振幅均随年龄增长而降低。在所有年龄组中,Rs1-/Y小鼠的APB分离的a波(a')振幅均降低。在暗适应的10Hz闪烁ERG中,Rs1-/Y小鼠的振幅-强度曲线下移。Rs1-/Y小鼠的ONL和IS/OS厚度降低。CAI减少了裂开的视网膜腔,但不影响ERG。
■除了接球后障碍,在Rs1-/Y小鼠中,感光细胞从早期年龄开始经历进行性功能障碍。长期CAI治疗改善了裂开性视网膜腔的收缩,而没有观察到功能改善。