Immunomodulation as a Neuroprotective Strategy for Glaucoma Treatment

Abstract

Purpose of review: This review aims to highlight the current knowledge about inflammatory mechanisms of neurodegeneration in glaucoma with emphasis on potential immunomodulation strategies.

Recent findings: Glaucomatous retina and optic nerve present multiple evidences of inflammatory responses of astroglia, microglia, and blood-born immune cells. Although adaptive/protective responses of resident or systemic immune cells can support neurons and promote tissue repair mechanisms after injurious insults, prolonged inflammatory processes can also produce neurotoxic mediators. Treatments targeting these neurodestructive outcomes may restore immune homeostasis and protect neurons from inflammatory injury. Due to widespread and chronic nature of neuroinflammation in glaucoma, immunomodulation offers a treatment strategy to protect different neuronal compartments of RGCs during the chronic and asynchronous course of neurodegeneration. Uncovering of distinct molecular responses and interactions of different immune cells that determine the neuroinflammatory phenotype and participate in neurodegenerative outcomes will be critical to develop effective strategies for immunomodulation in glaucoma.

Summary: Neuroinflammation has increasingly been recognized to play an important role in glaucomatous neurodegeneration, and its modulation appears to be a promising treatment strategy for neuroprotection.

Keywords: Glaucoma; immunomodulation; immunoregulation; neurodegeneration; neuroinflammation; neuroprotection.

Figure 1.

Glia-driven neuroinflammation may be initiated by both neuron injury (by DAMPs and ROS through PRRs, by ATP through mechanosensitive ion channels) and glaucoma-related insults, such as elevated intraocular pressure (through mechanosensitive ion channels). Thus, chronic tissue stress, neuron injury, glial and systemic immune responses, and sustained release of neurotoxic mediators create a vicious cycle that promotes further injury to retinal ganglion cells at different neuronal compartments.