Blog – Page 18

A decade ago, University at Buffalo researchers shed some light on an enduring neuroscience mystery: How exactly does a mutated huntingtin protein (HTT) cause Huntington’s disease?

They found that HTT is something like a traffic controller inside neurons, moving different cargo along neuronal highways called axons in concert with other proteins that are key for cellular function and survival. Reduce the amount of non-mutant HTT and you’ll create the neurological equivalent of traffic jams and roadblocks.

Now, the researchers have learned more about what can control the traffic-controlling HTT.

Individuals with retinal degenerative diseases struggle to restore vision due to the inability to regenerate retinal cells. Unlike cold-blooded vertebrates, mammals lack Müller glia (MG)-mediated retinal regeneration, indicating the limited regenerative capacity of mammalian MG. Here, we identify prospero-related homeobox 1 (Prox1) as a key factor restricting this process. Prox1 accumulates in MG of degenerating human and mouse retinas but not in regenerating zebrafish. In mice, Prox1 in MG originates from neighboring retinal neurons via intercellular transfer. Blocking this transfer enables MG reprogramming into retinal progenitor cells in injured mouse retinas. Moreover, adeno-associated viral delivery of an anti-Prox1 antibody, which sequesters extracellular Prox1, promotes retinal neuron regeneration and delays vision loss in a retinitis pigmentosa model. These findings establish Prox1 as a barrier to MG-mediated regeneration and highlight anti-Prox1 therapy as a promising strategy for restoring retinal regeneration in mammals.

---

Recovery for mammalian retinal degeneration is limited by a lack of Müller glia (MG)-mediated regeneration. Here authors show blocking Prox1 accumulation and intercellular transfer from retinal neurons enables MG reprogramming of retinal progenitor cells, promotes retinal neuron regeneration, and delays vision loss.