Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
J Ocul Pharmacol Ther. 2024 Jun;40(5):309-324. doi: 10.1089/jop.2023.0089. Epub 2024 Apr 11.
Glaucoma is a complex degenerative optic neuropathy characterized by loss of retinal ganglion cells (RGCs) leading to irreversible vision loss and blindness. has been used for decades in traditional medicine system. However, no extensive studies were reported on its antiglaucoma properties. Therefore, this study was designed to investigate the neuroprotective effects of extract on RGC against glaucoma rat model. High performance liquid chromatography and liquid chromatography tandem mass spectrometry was used to analyze the phytochemical profile of aqueous extract of (AESN). , {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} (MTT) and HDCFDA assays were used to determine cell viability and reactive oxygen species (ROS) production in Statens Seruminstitut Rabbit Cornea cells. , AESN was orally administered to carbomer-induced rats for 4 weeks. Intraocular pressure, antioxidant levels, and electrolytes were determined. Histopathological and immunohistochemical analysis was carried out to evaluate the neurodegeneration of RGC. MTT assay showed AESN exhibited greater cell viability and minimal ROS production at 10 μg/mL. Slit lamp and funduscopy confirmed glaucomatous changes in carbomer-induced rats. Administration of AESN showed minimal peripheral corneal vascularization and restored histopathological alterations such as minimal loss of corneal epithelium and moderate narrowing of the iridocorneal angle. Immunohistochemistry analysis showed increased expression of positive BRN3A cells and decreased matrix metalloproteinase (MMP)-9 activation in retina and cornea, whereas western blot analysis revealed downregulation of extracellular matrix proteins (COL-1 and MMP-9) in AESN-treated rats compared with the diseased group rats. AESN protects RGC loss through remodeling of MMPs and, therefore, can be used for the development of novel neurotherapeutics for the treatment of glaucoma.
青光眼是一种复杂的退行性视神经病变,其特征是视网膜神经节细胞 (RGC) 丧失,导致不可逆转的视力丧失和失明。 在传统医学体系中已经使用了几十年。然而,关于其抗青光眼特性的广泛研究尚未报道。因此,本研究旨在探讨 提取物对青光眼大鼠模型中 RGC 的神经保护作用。 高效液相色谱法和液相色谱串联质谱法用于分析 的水提物 (AESN) 的植物化学成分谱。 , {3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐} (MTT) 和 HDCFDA 测定用于确定 Statens Seruminstitut 兔角膜细胞中的细胞活力和活性氧 (ROS) 产生。 , AESN 口服给予卡波姆诱导的大鼠 4 周。测定眼内压、抗氧化水平和电解质。进行组织病理学和免疫组织化学分析以评估 RGC 的神经退行性变。 MTT 测定表明,AESN 在 10μg/mL 时表现出更高的细胞活力和最小的 ROS 产生。裂隙灯和眼底镜检查证实了卡波姆诱导的大鼠发生青光眼变化。AESN 给药显示最小的周边角膜血管化,并恢复了组织病理学改变,如角膜上皮最小损失和虹膜角膜角适度变窄。免疫组织化学分析显示,视网膜和角膜中 BRN3A 阳性细胞的表达增加,基质金属蛋白酶 (MMP)-9 激活减少,而 Western blot 分析显示,与患病组大鼠相比,AESN 治疗组大鼠细胞外基质蛋白 (COL-1 和 MMP-9) 的表达下调。 AESN 通过重塑 MMP 来保护 RGC 损失,因此可用于开发治疗青光眼的新型神经治疗药物。