Photoreceptor protection by mesencephalic astrocyte-derived neurotrophic factor (MANF)

Abstract

Retinal degenerations are a major cause of vision impairment and blindness. Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases.We investigated a novel neurotrophic factormesencephalicastrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed at a high level during postnatal development and the expression declines to a lower level as the retina matures. Müller cells are the major cells expressing MANF. It is also found in the retinal ganglion cells, in the inner nuclear layer (INL) neurons, and in retinal pigment epithelial (RPE) cells. Intravitreal injection of recombinant human (rh)MANF significantly protected rod and cone photoreceptors in rats carrying the rhodopsin S334ter mutation, and preserved electroretinograms (ERGs) in the rd10 (Pde6brd10/rd10) mice. These results indicate that MANF is a native protein in the retina and is a potent neurotrophic factor for photoreceptor protection.