Potential new approaches to treating AMD

Potential new approaches to treating eye diseases such as age-related macular degeneration (AMD) have been described in a new study from researchers at Genentech.

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. The researchers led by Hongkang Xi and Menno van Lookeren Campagne, of the Department of Immunology at Genentech in South San Francisco discovered that a pro-inflammatory signalling protein, or cytokine, called IL-33, plays a key role in recruiting phagocytes to damaged retina and inducing retinal degeneration.

Retinal cells release IL-33 in response to retinal injury

Working with rats and mice, Xi and colleagues found that specialised 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 researchers note.