Glycosylation in ocular surface health and disease

PROJECT SUMMARY/ABSTRACT Corneal nerves are responsible for transmitting sensory information to the brain, providing feedback on touch, pain, and temperature, and maintaining corneal health. Multiple studies have determined that corneal innervation is commonly impaired in corneal disorders leading to opacities and eventual vision loss. The underlying causes are diverse and include trauma, infection and inflammatory disorders. Unlike the central nervous system, the peripheral nervous system has the ability to undergo extensive regeneration. However, this process is slow, incomplete and, in the cornea, often leads to impaired sensory function and symptoms of ocular dryness and pain. This proposal focuses on the impact that glycosylation might have on corneal nerve regeneration and sensation. Research during the last decade has determined that glycans contribute to the formation and maintenance of nerves. It is becoming increasingly clear that abnormal glycosylation can alter nerve signaling and consequently contribute to the pathogenesis of peripheral nerve damage. However, despite these advances, we have a limited understanding of the types of glycans that are present in the trigeminal ganglion, which is responsible for providing innervation to the cornea, and their contribution to corneal sensation. We hypothesize that changes in glycan composition in the trigeminal ganglion following corneal injury will have important consequences to nerve regeneration and sensation, and could be potentially manipulated to treat neuropathic corneal pain. The following specific aims will address this objective: (1) to capture the complexity of protein glycans in the mouse trigeminal ganglion, (2) to determine glycan alterations in the mouse trigeminal ganglion following corneal injury, and (3) to examine the impact of altered fucosylation on corneal nerve repair, at the anatomical and functional levels. It is anticipated that the successful conclusion of this project will increase our understanding of the composition and function of glycans in the trigeminal ganglion, and advance the field of corneal nerve regeneration and sensation. These findings could also prove important to develop new strategies to promote functional reinnervation by targeting specific glycan metabolic pathways.