GHRH Agonist Boosts Macrophage Protection for Injured Optic Nerves

Optic nerve injury, often caused by trauma or diseases like glaucoma, leads to irreversible loss of retinal ganglion cells (RGCs), which are crucial for transmitting visual information to the brain. This RGC loss results in permanent vision impairment. While macrophages play a role in clearing debris and promoting repair after injury, their protective capacity is often insufficient. This study investigated whether an agonist of growth hormone-releasing hormone (GHRH) could enhance the neuroprotective functions of macrophages following optic nerve injury, thereby improving RGC survival.

The administration of the GHRH agonist significantly improved RGC survival compared to the vehicle-treated group. At two weeks post-injury, the treated group showed an average of 72% RGC survival, a substantial increase compared to the 45% survival observed in the control group (p<0.001). This neuroprotection was strongly correlated with altered macrophage activity. The GHRH agonist treatment led to a 2.8-fold increase in the number of beneficial M2-polarized macrophages and a 35% reduction in pro-inflammatory M1 macrophages within the injured optic nerve, indicating a shift towards a more reparative immune response. Furthermore, the treated animals exhibited a 1.9-fold upregulation of neurotrophic factors like BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) in the retina, suggesting enhanced local support for neuronal health. These findings demonstrate that GHRH agonism can effectively modulate the immune response to promote neuroprotection.