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胞磷胆碱和辅酶Q10:降低高眼压症中胶质细胞活化的治疗药物。

Citicoline and Coenzyme Q10: Therapeutic Agents for Glial Activation Reduction in Ocular Hypertension.

作者信息

Matamoros José A, Rubio-Casado Sara, Fernández-Albarral José A, Martínez-López Miguel A, Ramírez Ana I, Salobrar-García Elena, Marco Eva M, Paleo-García Victor, de Hoz Rosa, López-Cuenca Inés, Elvira-Hurtado Lorena, Sánchez-Puebla Lidia, Ramírez José M, López-Gallardo Meritxell, Salazar Juan J

机构信息

Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain.

Health Research Institute of the Hospital Clínico San Carlos (IdISSC) (ROR 014v12a39), 28040 Madrid, Spain.

出版信息

Pharmaceuticals (Basel). 2025 May 8;18(5):694. doi: 10.3390/ph18050694.

Abstract

: The loss of retinal ganglion cells (RGCs) is a hallmark of glaucoma, a major cause of blindness. Glial cell activation due to increased intraocular pressure (IOP) significantly contributes to RGC death. Therefore, substances with anti-inflammatory properties could help prevent that process. This study investigated whether combining Citicoline and Coenzyme Q10 (CoQ10) can reduce glial activation in the retina and the rest of the visual pathway, potentially preventing neurodegeneration in a mouse model of unilateral laser-induced ocular hypertension (OHT). Four groups of mice were used: vehicle (n = 12), CitiQ10 (n = 12), OHT-vehicle (n = 18), and OHT-CitiQ10 (n = 18). The administration of Citicoline and CoQ10 was performed orally once a day, initiated 15 days prior to the laser treatment and maintained post-treatment until sacrifice (3 days for retina or 7 days for the rest of the visual pathway). The retina, dorsolateral geniculate nucleus, superior colliculus, and visual cortex (V1) were immunohistochemically stained and analyzed. In the laser-CitiQ10 group, the Citicoline + CoQ10 compound revealed (1) an IOP decrease at 24 h and 3 days post-laser; and (2) reduced signs of macroglial (decreased GFAP area) and microglial (soma size, arbor area, microglia number, P2RY12 expression) activation in the retina and in the rest of the visual pathway (reduced activated microglial phenotypes and lower GFAP expression). This study shows that oral administration of Citicoline and CoQ10 can reduce glial activation caused by increased IOP in retina and visual pathway in a mouse model of OHT, potentially protecting RGCs from OHT-induced inflammation.

摘要

视网膜神经节细胞(RGCs)的丧失是青光眼的一个标志,青光眼是失明的主要原因。由于眼内压(IOP)升高导致的胶质细胞活化是RGC死亡的重要原因。因此,具有抗炎特性的物质可能有助于预防这一过程。本研究调查了联合使用胞磷胆碱和辅酶Q10(CoQ10)是否能减少视网膜和视觉通路其他部分的胶质细胞活化,从而有可能在单侧激光诱导性高眼压(OHT)小鼠模型中预防神经退行性变。使用了四组小鼠:溶剂对照组(n = 12)、胞磷胆碱 + CoQ10组(n = 12)、OHT-溶剂对照组(n = 18)和OHT-胞磷胆碱 + CoQ10组(n = 18)。胞磷胆碱和CoQ10通过口服给药,每天一次,在激光治疗前15天开始给药,并在治疗后持续给药直至处死(视网膜为3天,视觉通路其他部分为7天)。对视网膜、背外侧膝状体核、上丘和视觉皮层(V1)进行免疫组织化学染色和分析。在激光 - 胞磷胆碱 + CoQ10组中,胞磷胆碱 + CoQ10化合物显示:(1)激光后24小时和3天时眼压降低;(2)视网膜和视觉通路其他部分的大胶质细胞(GFAP面积减少)和小胶质细胞(胞体大小、树突面积、小胶质细胞数量、P2RY12表达)活化迹象减少(活化小胶质细胞表型减少和GFAP表达降低)。本研究表明,在OHT小鼠模型中口服胞磷胆碱和CoQ10可减少视网膜和视觉通路中由IOP升高引起的胶质细胞活化,有可能保护RGCs免受OHT诱导的炎症影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc9/12114817/4721b704f0c0/pharmaceuticals-18-00694-g001.jpg

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