Corneal nerve regeneration

Dry eye disease (Keratoconjunctivitis sicca) occurs as a result of a disturbed tear secretion e.g. due to impairment of the lacrimal gland. Besides other reasons, this can occur due to a dysfunction in the sensory feedback mechanism of the sub-basal nerve plexus, as a result of trauma or infection. Patients may experience deterioration of, or even complete loss of visual acuity (Tutt, Bradley et al. 2000). Some diseases mainly affect the nerve plexus but neurotrophic keratopathy, a severe degenerative disease affecting the integrity of the cornea, can also result from impairment of the trigeminal nerve. The sub-basal nerve plexus may also be damaged during refractive surgery (e.g. LASIK) or corneal transplantation. Studies have confirmed a nerve fibre loss of nearly 90% after LASIK with a subsequent slow recovery of the nerve density reaching only 50% at one year post-surgery.

Often, it is not possible to treat the cause of corneal diseases using drug therapies alone. To preserve visual function, a microsurgical procedure is often inevitable. Amniotic membrane has been widely used but has some disadvantages such as biological variation between donors, possible disease transmission and limited transparency, and so a replacement of this tissue is desirable. Our group has established two different scaffolds (keratin films and plastic compressed collagen (PCC) as an alternative for amniotic membrane in conjunctiva and cornea (Reichl, Borrelli et al. 2011, Borrelli, Reichl et al. 2013, Borrelli, Joepen et al. 2015, Drechsler, Kunze et al. 2015) and tested them successfully in vivo. In these different scaffolds, nerve reinnervation is desirable and is one important part of this project.

The aim of this project is to analyse corneal nerve regeneration in healthy cornea and following implantation of various bioactive scaffolds that may enhance the regenerative. To achieve this, we use dorsal root ganglion cells (DRGs) as a model system and perform in vitro analysis comprising functional assays (proliferation, adhesion), using cell and molecular biology methodologies. We also intend to test efficacy in vivo in a murine model. 

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