Optic Nerve Repair

Glaucoma kills neurons in the optic nerve and causes blindness. Repairing neurons that send visual information from the eye to the brain is a challenge for two reasons: neurons don’t spontaneously regenerate after injury, and proteins in the optic nerve can impede their growth. Recent discoveries have identified ways to trigger regeneration in neurons, but inhibitory proteins still prevent them from reaching the brain. My PhD work targeted these proteins by digesting and neutralizing their inhibitory sugar chains with an enzyme called arylsulfatase B. By combining this treatment with a regeneration trigger, we hope to enable neurons to grow farther, connect with the brain, and ultimately restore vision.

Using the enzyme arylsulfatase B (ARSB) to remove sulfate groups (4S) from the ends of chondroitin sulfate proteoglycans (CSPGs) enhanced RGC axon regeneration in the presence of an intrinsic pro-regenerative stimulus (Zymosan). Modification of the CSPGs alone, with ARSB or a similar enzyme, ChABC, was insufficient to stimulate regeneration. Intrinsic modification of RGCs with Zymosan and other stimuli combined in an additive fashion to collectively promote axon regeneration, especially in combination with ARSB.

Using the enzyme arylsulfatase B (ARSB) to remove sulfate groups (4S) from the ends of chondroitin sulfate proteoglycans (CSPGs) enhanced RGC axon regeneration in the presence of an intrinsic pro-regenerative stimulus (Zymosan). Modification of the CSPGs alone, with ARSB or a similar enzyme, ChABC, was insufficient to stimulate regeneration. Intrinsic modification of RGCs with Zymosan and other stimuli combined in an additive fashion to collectively promote axon regeneration, especially in combination with ARSB.

 
The optic pathway of a mouse has been removed and sectioned for imaging on a fluorescence microscope. Astrocyte cells are visible throughout the optic pathway.

The optic pathway of a mouse has been removed and sectioned for imaging on a fluorescence microscope. Astrocyte cells are visible throughout the optic pathway.