Introduction
The cornea is one of the most densely innervated tissues in the body. Along with their sensory function, corneal nerves contribute to the trophic status of corneal tissue. Thus, corneal denervation, accidental or due to disease, compromises tissue integrity, causing the so-called neuroparalytic keratitis (a clinical condition with spontaneous corneal ulcers, eye pain, and eventually blindness due to loss of corneal transparency).
Myelinated sensory axons lose their myelin sheaths upon entering the corneal stroma, continuing as unmyelinated axons to allow transparency of the cornea. Even being non-myelinated, stromal axons are covered by Schwann cells, which have a neurotrophic effect mediated by growth factors. In CORNER2 we study the role of corneal Schwann cells (SC) in reinnervation after corneal injury. We will use several genetically modified mice generated in our previous CORNER project (PROMETEO/2018/114), in which the CS and corneal nerves are marked with different fluorescent proteins, and which allow the selective elimination of the CS in adult animals.
As a result of CORNER project, we identified a new type of CS in the corneal stroma. These cells are not aligned with the axons nor do they have obvious physical contact with them. In CORNER2 project we will determine, using NGS technologies, the gene expression pattern that characterizes those axon-unassociated CS and explore its contribution to pain transduction and corneal sensitivity.
In addition, we will determine the role of CS in the structure and function of the innervation of the human cornea. We will characterize the distribution and density of corneal nerves using in vivo confocal microscopy and we will explore corneal sensitivity, using a gas aesthesiometer, in patients with Charcot-Marie-Tooth disease type 1 (CMT1), who present mutations that alter the biology of the CS. This will also allow us to identify possible alterations in non-symptomatic people carrying mutations.
The results of CORNER2 will precisely define neuroglial interactions and their effects on corneal reinnervation capacity. It will also help to understand the impact that CMT1 mutations, which alter CS function, have on peripheral nerves, making it possible to identify neural defects in subclinical stages and, consequently, establish early diagnosis and initiation of preventive treatments in non-symptomatic carriers of CMT1 mutations.
