Growth hormone reduces retinal inflammation and preserves microglial morphology after optic nerve crush in male rats

Jerusa Balderas-Márquez¹David Epardo¹Lourdes Siqueiros-Márquez¹Martha Elizabeth Carranza¹Maricela Luna Muñoz¹José Luis Quintanar²Carlos Arámburo^1*Carlos Guillermo Martínez-Moreno^1*

• ¹Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, Mexico
• ²Universidad Autonoma de Aguascalientes Centro de Ciencias Basicas, Aguascalientes, Mexico

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 hours and 14 days post-ONC, with or without GH treatment (0.5 mg/kg, subcutaneously, every 12 hours). 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.