Yep. New Application for MANF - not the same old news people : Regeneration and repair are critical to ensure tissue health throughout life. We are exploring the role of hemocytes in the control of photoreceptor survival and tissue repair in the fly retina. Hemocytes are attracted to the pupal retina and activated by Pvf-1/PvR signaling in response to UV-induced DNA damage, and are required to prevent excessive cell loss. We are now using this system to identify hemocyte-derived factors that can promote tissue repair in the retina, and are testing the conservation of their function in the mammalian retina. We have identified MANF (Mesencephalic Astrocyte-derived Neurotrophic Factor), as a hemocyte derived protein in Drosophila that can promote retinal repair. We find that MANF is induced in hemocytes in response to stress in a Pvf-1/PvR dependent manner, is secreted into the hemolymph, and reduces tissue loss after UV-induced and genetically triggered photoreceptor apoptosis. Moreover, stress-induced MANF results in changes in the hemocyte population that correlate with increased lamellocyte differentiation. Based on these observations, and on the reported cytoprotective function of MANF in the mammalian brain, we hypothesize that MANF has a conserved role in mammals, and that this function can promote integration of transplanted retinal cells into the diseased retina. We find that mouse MANF is induced in microglia and macrophages invading the retina following light damage, and that this correlates with reduced tissue loss. Importantly, intravitreal delivery of MANF recombinant protein is sufficient to limit photoreceptor death following light damage, and promotes beneficial M2 polarization of macrophages/microglia, suggesting that the role of MANF is conserved between flies and mice. Further, we will test the ability of MANF delivery in promoting progenitor cell integration following transplantation. This work will serve as a proof of concept for the use of factors that promote tissue repair as co-adjuvants in stem cell regenerative therapies, and for the use of the fly as a tool to identify such factors.
From Buck institute's abstract
