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Victor H Guaiquil, Qiang Zhou, Yuncin Luo, Tara Nguyen, Mark Rosenblatt; Semaphorin3A induces nerve regeneration in the adult cornea-a switch from its repulsive role in development.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4418.
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© ARVO (1962-2015); The Authors (2016-present)
Determine the neuro-regenerative potential of semaphorin3A (Sema3A), an axon guidance and neuro repellent factor highly expressed upon cornea injury.
The expression of Sema3A in the cornea was evaluated by qPCR and immunostaining. The effects of Sema3A on peripheral nerve system neurons such as those that innervate the cornea was studied in vitro in embryonic and adult isolated trigeminal ganglia (TG) and dorsal 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 containing Sema3A. Neuronal growth was evaluated using Neurolicida software.
The gene expression profile of the Semaphorin class 3 family members shows that all are expressed in the cornea. However, upon cornea injury there is a fast increase in Sema3A expression. We corroborated that Sema3A totally abolished the growth promoting effect of nerve growth factor (NGF) on embryonic neurons and observed signs of growth cone collapse and axonal retraction after 30 min of Sema3A addition. However, in adult isolated TG or DRG neurons, Sema3A did not inhibited the NGF-induced neuronal growth. Furthermore, adult neurons treated with Sema3A alone produced similar neuronal growth to cells treated with NGF and the length of the neurites and branching was comparable between both treatments. These effects were replicated in vivo, where thy1-YFP neurofluorescent mice subjected to cornea epithelium debridement and receiving intrastromal pellet implantation containing Sema3A showed increased corneal nerve regeneration than those receiving pellets with vehicle.
In adult PNS neurons, Sema3A is a potent inducer of neuronal growth in vitro and cornea nerve regeneration in vivo. Our data indicates a functional switch for the role of Sema3A in PNS neurons where the well-described repulsive role during development changes to a growth promoting effect during adulthood. The high expression of Sema3A in the normal and injured adult corneas could be related to its role as a growth factor.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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