In the present study, researchers investigated a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina

Retinal degenerations are a major cause of vision impairment and blindness. Retinitis pigmentosa (RP), a most common inherited retinal degeneration, affects one in 3500–4000 people. Mutations in more than at least 60 genes (as of February 2018) are identified to be associated to RP. In many RP cases, the causative mutations remain unidentified.

Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases. Researchers have investigated a novel neurotrophic factor mesencephalic astrocyte-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 provide experimental evidence to consider MANF as a neuroprotective agent for photoreceptor degenerative disorders, including RP and age-related macular degeneration. Further studies to understand the function of MANF N-domain could shed light on the extracellular neurotrophic activity of MANF.

Identifying the cell surface receptors of MANF could lead to a better understanding of the molecular mechanism(s) that mediate MANF neurotrophic activity.

This is a study of high translational value to examine the neuroprotective potential of a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed in the retina at the high level during postnatal development and then declines as the retina matures.

Recombinant MANF protects rod and cone photoreceptor cells and preserves electroretinograms (ERGs). These results suggest a role of MANF in the retinal development and provide preclinical evidence for further development of MANF as a neuroprotective agent as a potential treatment for retinal degenerative disorders.