Investigating regenerative potential of retinal cells

Zhang and co-principal investigators Sheng Ding, PhD, from The Scripps Research Institute, and Thomas Reh, PhD from the University of Washington, received the highest possible scores for their proposal to investigate the regenerative potential of retinal cells, resulting in a $4.66 million NIH Transformative Award. Their long-term goal is to restore visual function lost through diseases such as macular degeneration and retinitis pigmentosa.

“The success of this work could mean a paradigm shift in how retinal disease is treated, and could have broad and profound impact on human disease therapies by utilizing the regenerative power of our own cells,” said Zhang.

Some vertebrates, such as goldfish and newts, have a remarkable ability to regenerate a lost limb or eye - something it was thought no mammal can do. However, they recently showed proof of principle at a small-scale level in mice by turning Muller cells into a type of retinal neuron.

“The human genome is quite similar to that of a newt, but we humans seem to have lost the potential to regenerate our own cells, possibly due to some inhibitory mechanims,” Zhang said. “We are seeking small molecule chemicals that can block these inhibitions and consequently unlock humans' regenerative potential.”

The researchers are looking at particular kinds of cells called Muller cells, which are abundant and have the ability to regenerate nerve cells after retinal injury in fish, they usually play a supporting role in the central nervous system neurons of humans, such as those present in the eye or brain. This study proposes to use chemicals to turn Muller cells into photoreceptors in the eye - cells that are lost in two diseases that are leading causes of blindness, macular degeneration and retinitis pigmentosa.

Identification of chemicals for Muller cells reprogramming and differentiation will provide new avenues in developing cell-based therapy as well as small molecule drugs for regenerative medicine, and facilitate new understanding of the mechanisms of trans-differentiation, according to the scientists. They plan to screen more than 100,000 compounds in order to identify the chemicals that prompt mouse Muller glia to develop new neurons, conferring the power of regeneration to the mammalian retina.