Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis

Area of Science:

• Ophthalmology
• Neuroscience
• Immunology

Background:

• Optic nerve crush (ONC) models optic nerve injury and retinal ganglion cell (RGC) death, partly mediated by microglia-secreted cytokines.
• Glaucoma datasets indicate Ccr5 (CC chemokine receptor type 5) is linked to RGC injury.

Purpose of the Study:

• To investigate the role of the CCL5/CCR5 pathway in RGC damage.
• To evaluate maraviroc, a CCR5 inhibitor, as a potential therapeutic agent for optic nerve injury.

Main Methods:

• Bioinformatic analysis of glaucoma datasets (GSE142881, GSE26299).
• Utilized the ONC animal model with immunofluorescence, TUNEL staining, OCT, and electrophysiology.
• Assessed mechanisms via co-culture of neuro2a and BV2 cells; evaluated intravitreal maraviroc safety and efficacy.

Main Results:

• CCR5 expression correlated significantly with RGC injury.
• Maraviroc treatment preserved RGC structure, ganglion cell complex (GCC) thickness, and retinal function in the ONC model.
• CCR5 inhibition prevented Cathepsin S (CTSS) downregulation and apoptosis, and intravitreal maraviroc was safe and effective.

Conclusions:

• Microglial activation in glaucoma upregulates CCL5, leading to CCR5-mediated RGC apoptosis.
• Maraviroc effectively reduces RGC death and optic nerve damage.
• Maraviroc presents a promising neuroprotective strategy for optic nerve injury treatment.