Glaucoma is a heterogeneous group of irreversible and blinding optic neuropathies caused by multiple factors. It is clinically characterized by progressive loss of visual field and decline in visual acuity, ultimately culminating in complete blindness. Hallmark pathological features include progressive degeneration of retinal ganglion cells and atrophy of the optic nerve. Importantly, the pathological process of glaucoma extends far beyond the eyeball, involving transsynaptic degeneration across the entire visual pathway. Microglia, as the principal immune regulators of the central nervous system, serve as the earliest sensors and effectors in the pathogenesis of glaucoma. By modulating synaptic plasticity, microglia contribute to synaptic loss and the disruption of neural circuits. They also play essential roles in maintaining neural tissue homeostasis. This review summarizes current evidence and underlying mechanisms of bidirectional transsynaptic degeneration in glaucoma. It highlights that targeting microglial functional homeostasis, particularly their regulation of synaptic plasticity, may be a promising strategy to mitigate glaucoma-associated transsynaptic degeneration and promote central neuroprotection.
He et al. (Thu,) studied this question.