Rashid Khan Mohammad, Fayaz Ahmad Sheikh, Nadeem Ahmed, Imam Faisal, Al-Harbi Naif O, Shahnawaz Khan Mohd, Alsahli Meshal, Alhosaini Khaled
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Saudi Arabia.
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2023 Jan;31(1):147-153. doi: 10.1016/j.jsps.2022.11.013. Epub 2022 Nov 23.
The complicated multiple sclerosis (MS) can exhibit subacute sight deterioration and can lead to total deprivation of vision. In the current work, we explored the therapeutic outcome of Cathepsin B inhibitor (CA-074) against retinopathy and optic neuritis (ON) caused by experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP) in female SJL/J mice. A daily dose of 10 mg/kg CA-074 was administered to the EAE mice intraperitoneally for 14 days from day 14 post-immunization until day 28. The Western blot and immunofluorescence analyses show inflammation in the optic nerve through the elevation of iNOS and NFkB markers in EAE mice. Optic neuritis was reported which is a consequence of demyelination and axon injury, estimated with the reduction in myelin basic protein (MBP). The glial fibrillary acidic protein (GFAP) expression level was found to be elevated in the retina of EAE mice which confirmed the retinopathy. The administration of CA-074 ameliorated optic neuritis and retinopathy by reducing inflammation. The treatment with CA-074 also reduced the demyelination and axonal injuries in the EAE mice. The findings of this study have shown the protective effect of CA-074 in the case of retinopathy and ON inflicted by EAE in SJL/J mice.
复杂型多发性硬化症（MS）可表现为亚急性视力减退，并可导致完全失明。在当前研究中，我们探究了组织蛋白酶B抑制剂（CA-074）对雌性SJL/J小鼠中由蛋白脂蛋白肽（PLP）诱导的实验性自身免疫性脑脊髓炎（EAE）所引起的视网膜病变和视神经炎（ON）的治疗效果。从免疫后第14天至第28天，每天以10 mg/kg的剂量给EAE小鼠腹腔注射CA-074，持续14天。蛋白质印迹法和免疫荧光分析显示，EAE小鼠视神经中诱导型一氧化氮合酶（iNOS）和核因子κB（NFkB）标志物升高，存在炎症。据报告出现了视神经炎，这是脱髓鞘和轴突损伤的结果，可通过髓鞘碱性蛋白（MBP）的减少来估计。发现EAE小鼠视网膜中胶质纤维酸性蛋白（GFAP）表达水平升高，证实存在视网膜病变。CA-074的给药通过减轻炎症改善了视神经炎和视网膜病变。CA-074治疗还减轻了EAE小鼠的脱髓鞘和轴突损伤。本研究结果表明，CA-074对SJL/J小鼠中EAE所致的视网膜病变和视神经炎具有保护作用。
