Newswise,
April 5, 2016— Potential new approaches to treating eye diseases such as
age-related macular degeneration (AMD) are described in a new study, “IL-33
amplifies an innate immune response in the degenerating retina,” in the
February Journal of Experimental Medicine.
AMD
is a leading cause of vision impairment in old age, and is caused by the
degeneration of cells in the retinal layer of the eye. Retinal cell death can
be induced by phagocytic immune cells that infiltrate the tissue in response to
injury or infection, but the molecular signals that trigger phagocyte invasion
are largely unknown.
A
team of researchers led by Hongkang Xi and Menno van Lookeren Campagne, of the
Department of Immunology at Genentech, Inc., in South San Francisco, Calif.,
discovered that a pro-inflammatory signaling protein, or cytokine, called
IL-33, plays a key role in recruiting phagocytes to damaged retina and inducing
retinal degeneration.
Working
with rats and mice, Xi and colleagues found that specialized retinal cells
called Müller glial cells release IL-33 in response to retinal injury.
The
cytokine then binds to its receptor on the surface of the Müller cells and
induces the release of additional inflammatory proteins that attract phagocytes
to the damaged retina. Blocking the IL-33 receptor inhibited this process and
prevented injury-induced retinal degeneration.
The
researchers also found that IL-33 levels are increased in the retinas of AMD
patients, suggesting that the same pathway may occur in humans. Inhibiting
IL-33 may therefore help treat AMD and other retinal degenerative diseases.
“This
study for the first time shows increased expression of IL-33 in AMD and further
demonstrates a role for glia-derived IL-33 in the accumulation of myeloid cells
in the outer retina, loss of photoreceptors, and functional impairment of the
retina in preclinical models of retina stress,” the authors note.
