Balderas-Márquez Jerusa E, Epardo David, Siqueiros-Márquez Lourdes, Carranza Martha, Luna Maricela, Quintanar José Luis, Arámburo Carlos, Martínez-Moreno Carlos G
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Ags, Mexico.
Front Cell Neurosci. 2025 Sep 5;19:1636399. doi: 10.3389/fncel.2025.1636399. eCollection 2025.
This study investigates the neuroprotective role of growth hormone (GH) in modulating retinal inflammation and microglial responses following optic nerve crush (ONC) in male rats.
Retinal inflammation and microglial activation were assessed at 24 h and 14 days post-ONC, with or without GH treatment (0.5 mg/kg, subcutaneously, every 12 h). Gene and protein expression of inflammatory markers (e.g., IL-6, TNFα, Iba1, CD86, CD206) were evaluated using qPCR, ELISA, and Western blotting. Microglial morphology was quantified using skeleton and fractal analysis of Iba1-stained retinal sections. Retinal structure and function were assessed via fundus imaging and optomotor reflex testing.
ONC induced significant increases in proinflammatory cytokines (IL-6, TNFα, IL-18) and microglial activation, characterized by reduced branching complexity and increased cell density. GH treatment significantly decreased proinflammatory cytokine levels, modulated microglial phenotype (CD86/CD206 expression), and preserved microglial morphology in the retina. Using the SIM-A9 microglial cell line, we further demonstrated that GH reduces NFκB pathway activation and suppresses LPS-induced proinflammatory cytokine production. At 14 days post-injury, GH-treated retinas exhibited reduced optic nerve size and improved optomotor responses, indicating both structural neuroprotection and functional recovery.
Overall, GH mitigates ONC-induced retinal inflammation by reducing proinflammatory signaling and preserving microglial architecture, thereby protecting retinal integrity and function. These findings highlight the potential of GH as a therapeutic agent for retinal neurodegenerative conditions.
本研究调查了生长激素（GH）在调节雄性大鼠视神经挤压伤（ONC）后视网膜炎症和小胶质细胞反应中的神经保护作用。
在ONC后24小时和14天评估视网膜炎症和小胶质细胞激活情况，分为接受或不接受GH治疗组（0.5毫克/千克，皮下注射，每12小时一次）。使用qPCR、ELISA和蛋白质印迹法评估炎症标志物（如IL-6、TNFα、Iba1、CD86、CD206）的基因和蛋白质表达。使用对Iba1染色的视网膜切片进行骨架和分形分析来量化小胶质细胞形态。通过眼底成像和视动反射测试评估视网膜结构和功能。
ONC导致促炎细胞因子（IL-6、TNFα、IL-18）显著增加以及小胶质细胞激活，其特征为分支复杂性降低和细胞密度增加。GH治疗显著降低促炎细胞因子水平，调节小胶质细胞表型（CD86/CD206表达），并保留视网膜中小胶质细胞的形态。使用SIM-A9小胶质细胞系，我们进一步证明GH可降低NFκB途径的激活并抑制LPS诱导促炎细胞因子的产生。在损伤后14天，接受GH治疗组的视网膜视神经尺寸减小且视动反应改善，表明具有结构神经保护和功能恢复作用。
总体而言，GH通过减少促炎信号传导和保留小胶质细胞结构来减轻ONC诱导的视网膜炎症，从而保护视网膜完整性和功能。这些发现突出了GH作为视网膜神经退行性疾病治疗药物的潜力。
