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Victor H Guaiquil, Qiang zhou, Yuncin Luo, Tara Nguyen, Mark Rosenblatt; Semaphorin3A is an inducer of neuronal growth and nerve regeneration in adult corneas.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):141.
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© ARVO (1962-2015); The Authors (2016-present)
Determine the neuro-regenerative potential of semaphoring3A, an axon guidance and neuro repellent factor highly expressed upon cornea injury.
The effect of semaphorin3A (Sema3A) on peripheral nerve system neurons such as those that innervate the cornea was studied in vitro in isolated trigeminal ganglia (TG) and dorso root ganglia (DRG) neurons. Neurons were treated with neuronal growth factor (NGF) to induce neurite growth and then exposed to Sema3A to evaluate growth cone collapse and axonal retraction. Neuronal cultures were treated with Sema3A alone in a time and dose dependent manner to determine neuronal growth induction. In vivo, thy1-YFP neurofluorescent mice were used to visualize nerve regeneration in corneas subjected to epithelium debridement and intrastromal pellet implantation. Neuronal growth was evaluated using Neurolicida software.
NGF induced strong neurite growth in both TG and DRG neurons. In embryonic DRG neurons, the effect of NGF was totally abolished by Sema3A and growth cone collapse and axonal retraction was visible after 30 min of incubation. In adult DRG, no inhibition of neuronal growth or collapse was observed even at high concentration of Sema3A. This was also observed in adult TG neurons. When Sema3A was added to untreated isolated neurons, it induced strong neurite elongation and branching. These effects were replicated in vivo and animals receiving pellets containing Sema3A presented increased nerve regeneration than those having pellets with vehicle.
The high expression of Sema3a in the normal and injured adult cornea could be related to their role as a growth factor and in embryonic tissue, related to their axonal repellent properties.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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