Corneal epithelial and neuronal interactions: Role in nerve regeneration and wound healing

• Applicant: Dr. Bhavani S. Kowtharapu
• Subject Area: Ophthalmology
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 268533233

In the cornea, on-going communication between the corneal epithelium and trigeminal sensory nerve endings is indispensable for the proper functioning of the epithelium. Impaired corneal innervation and sensitivity are the main causes of corneal neurotrophic keratopathy which simultaneously also leads to poor epithelial wound healing. Regeneration of the disrupted nerve endings and renewal of the proper epithelium is essential to restore the corneal sensitivity and it is necessary, in this context, to investigate corneal epithelial and trigeminal neuron interactions at the molecular level to shed light on specific individual molecules and their role in corneal wound healing and nerve regeneration during neurotrophic keratopathy. Previously, we have studied the effect of corneal epithelial cells on trigeminal neurons as well as the effect of trigeminal neurons on corneal epithelial cells during wound healing in a murine model system. We observed an increase in the substance P (SP) mRNA expression in trigeminal sensory neurons and a decrease in the expression of bone morphogenetic protein 7 (BMP7) mRNA in corneal epithelial cells in the presence of the other cell-type. This study confirms the existence of communication between corneal epithelial cells and trigeminal sensory neurons and opens up new dimensions to further study the effect of these molecules during nerve regeneration and wound healing. Present study aims to study the effect of SP and BMP7 on epithelial and sensory neuron functions using cultured primary human corneal epithelial cells and trigeminal neurons along with identification of novel targets related to wound healing and nerve regeneration. Dissecting the underlying mechanisms of activated signaling pathways during corneal wound healing and nerve regeneration, using primary human cell culture model systems, in the presence of SP and BMP7 may enable designing of future target specific therapeutics for the treatment of ocular diseases.

• DFG Programme: Research Grants
• Co-Investigator: Professor Oliver Stachs, Ph.D.