Restoring Sight To The Blind

Credit: Wei Li, National Eye Institute, National Institutes of Health. Part of the exhibit Life:Magnified by ASCB and NIGMS

A series of experiments have succeeded in partially regenerating optic nerve cells in mice

There are multiple layers of cells within the eye responsible for capturing light information, and transmitting this visual data through the optic nerve to the brain. Among these are retinal ganglion cells, of which there are up to 30 types, and they effectively process the range of different visual information passed to them. These ganglion cells produce axons - projections that conduct and communicate electrical impulses. Axons are crucial for transmitting visual data to the brain; if this connection is severed the consequence is blindness.

Regrowing connections

End stage glaucoma. Credit: Heiko Philippin, Community Eye Health Journal Vol. 25 No. 79.80 2012

After cataracts, glaucoma is the most common form of blindness and affects around 70 million worldwide - causing pressure on the optic nerve and impairing connections. The optic nerve can also be severed as a result of injury or cancer, and there is currently no way of restoring sight in such cases. While adult axons in most regions of the body are rather poor at regenerating, in early development axons have an extraordinary ability to make their way through the brain to their target. If we could find a way trigger this ability again, we might be able to repair the optic nerve and thus restore vision. 

Re-activating mTOR

Activity of mTOR, a pathway involved with growth and proliferation, declines within these cells during the aging process.  In a bid to test whether re-activating mTOR in these retinal ganglion cells could trigger new axon growth, researchers exposed mice with one crushed optic nerve to either high contrast visual stimulation, or biochemical activation of mTOR. Both strategies produced some new axonal growth, but both combined, in conjunction with blocking of the other healthy eye, produced substantial new axonal growth that proved able to migrate to the correct brain regions too. 

"Somehow these retinal ganglion cells' axons retained their own GPS systems. They went to the right places, and they did not go to the wrong places"

Amazingly, this combination approach proved able to successfully transmit enough visual information for the mice to see an expanding dark circle, similar to the approach of a bird of prey, and run to a hiding place in response.  

Mouse retinal ganglion cell axons (magenta and green) extending from site of optic nerve injury. Credit: Andrew D. Huberman

A partial success

While the experiments were able to regenerate sight to an extent, the mice still failed finer visual discrimination tests - suggesting that while new connections had been formed in the brain, the number may have been fairly limited or even confined to a certain subtype of ganglion cells. The research is still very encouraging however, and suggests that modulating the mTOR pathway together with stimulation may be an effective strategy against conditions such as glaucoma. 

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