Attempting to Improve the Effectiveness of Retinal Cell Therapies

Transplantation of new retinal cells is one of the potential approaches to treat age-related loss of vision, such as that resulting from macular degeneration, in which photoreceptor cells die for a variety of reasons. The effectiveness of these approaches is so far limited, however, as most transplanted cells die. Researchers here investigate a means of improvement:

Regenerative therapies, based on cell replacement, hold promise for a wide range of age-related diseases, but efforts to bring the therapies to patients have not been very successful - in large part because the newly-derived replacement cells can't integrate efficiently into tissues affected by the ravages of aging. However, researchers have now harnessed a naturally-occurring and evolutionarily ancient anti-inflammatory mechanism that repaired the eye and significantly enhanced the success of retinal regenerative therapies in mice.

The group discovered a previously unknown immunomodulatory property of an evolutionarily conserved factor, MANF (Mesencephalic Astrocyte-derived Neurotrophic Factor). MANF converts inflammatory immune cells into repairing immune cells; in this study it profoundly improved the endogenous repair capacity of the retina in both flies and mice. Strikingly, when the researchers used MANF as a supplement while transplanting photoreceptors into congenitally blind mice, MANF increased the efficiency of integration and accelerated and improved the recovery of visual function. Even though researchers around the world have successfully transplanted retinal stem cells in mice that success has not benefited the millions of people who suffer from vision problems related to retinal degeneration, because only about 1 percent of the transplanted cells survive and integrate over time. "We are hoping to turn that statistic around."

The research also raises the possibility of using MANF as a treatment early in the disease process as a way of preventing further symptoms from developing, noting that they used MANF to protect photoreceptors in three mouse models of photoreceptor degeneration. "Our hope is that MANF will be useful for treatment of inflammatory conditions in many disease contexts. Focusing on immune modulation to promote a healthy repair response to tissue damage rather than a deleterious inflammatory response is a new frontier in aging research."



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