The Role of Semaphorin/Neuropilin Signaling in the Development of Innervation and Avascularization of the Cornea
Lwigale, Peter Yunju
Doctor of Philosophy
Millions of corneal procedures performed every year and a multitude of corneal diseases can damage the corneal nerves or induce neovascularization into the cornea; a complete understanding of the molecular regulators of nerve and blood growth into the cornea is necessary to help keep this tissue properly innervated and avascular during a disease state. Identifying the developmental regulators that establish avascularity and innervation have great potential for therapeutic use in the adult. The development of corneal innervation has only been studied in the avian system, but current molecular investigations into regulators of innervation and avascularity are done in the mammalian system. I performed a detailed analysis of the development of mammalian corneal innervation. This information can now be used for any future studies in this area. My work has also identified molecular regulators that help to control the development of corneal innervation and vascularization in both the avian and mammalian system. Semaphorin3A (Sema3A) is a known axon repellent and inhibitor of endothelial cell migration. This protein is known to affect avian cornea development, but it is unknown if this molecule affects mammalian cornea development or avascularity. Through the use of immunostaining, in situ hybridization, qRT-PCR, genetic and pharmacological inhibition of Sema3A, and implantation of recombinant Sema3A, I have discovered that Sema3A plays a key role in the timing of innervation into the mammalian cornea, and the development of an avascular cornea in both the avian and mammalian systems. This is the first time Sema3A has shown to be essential in both the mammalian cornea development and in establishing an avascular cornea. This information could serve as a springboard for further investigation into potential therapeutic drugs for diseases of cornea innervation or neovascularization.
Cornea development; Semaphorin; Neuropilin; Innervation; Avascurlarity