Astrocytes are a type of glial cell which form the majority of cells in the human central nervous system (CNS). In the retina they occur exclusively in the ganglion cell layer, mixed with retinal ganglion cells (RGCs).
In response to local or systemic stimuli,
the astrocytes (A1 and A2) adopt reactive forms.
The A1 astrocytes develop pro-inflammatory
and neurotoxic functions. They lose their phagocytic capacity, and their
ability for synapse formation and function.
A2 astrocytes upregulate neurotrophic
factors, promoting a neuroprotective environment.
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ASTROCYTES IN GLAUCOMA |
Sterling and associates have shown that
ocular hypertension can trigger microglia to produce and release pro-inflammatory
cytokines C1q, interleukin-1α
(IL-1α), and tumor necrosis factor-α (TNF-α).
These three cytokines are necessary and sufficient to drive the formation of A1
astrocytes.
Studies have demonstrated a strong association
between the above mentioned three cytokines and glaucoma. IL-1α and TNF
polymorphisms are associated with primary open angle glaucoma. TNF-α protein
levels are elevated in the vitreous, retina, and optic nerves of glaucomatous
eyes. In the DBA/2J mouse model of hypertensive glaucoma, C1qa mRNA levels are
associated with disease progression, and C1q inhibition is sufficient to
prevent early RGC synapse loss and RGC death.
Glucagon-like peptide-1 is an incretin
hormone that regulates blood glucose, weight, and satiety through its action at
the glucagon-like peptide-1 receptor (GLP-1R) in both the systemic circulation
and the central nervous system. NLY01 is a long-acting GLP-1R agonist with an
extended half-life and favorable blood brain barrier penetration.
Sterling has shown NLY01 therapy reduces
the production of C1q, TNF-a, and IL-1a by the CD11b+ CD11c and CD11b+ CD11c+
dendritic cells in a mouse model of glaucoma. It also reduces A1 astrocyte
transformation and RGC loss.
Therefore, NLY01 has potential clinical use
in the treatment of glaucoma and possibly other retinal diseases characterized
by reactive astrogliosis.
