Zoomed in picture of an eye

CorneaRegID

Cornea regeneration instructed by molecular cell identity characterisation
Duration
2021 until 2025
Project member(s)
Arts, J.A. (Julian) Dr Zhou, H. (Jo Huiqing) Dr Laberthonnière, C.A.J. (Camille) , Vanessa Lapointe (Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine) , Marco Schaafsma (Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine) , Mor Dickman (Maastricht UMC+, University Eye Clinic)
Project type
Research

Cornea damage can lead to blindness and severely impair a patient's quality of life. The state-of-the-art treatment is a stem cell-based transplantation therapy that requires limbal stem cells (LSCs) from the patient's uninjured eye to regenerate the transparent cornea. For patients with two injured eyes, this treatment becomes impossible and blindness follows. We propose to develop a novel approach for efficient corneal regeneration by transdifferentiating other cell sources of the patient such as skin or oral mucosa, thereby restoring vision and preventing blindness.

The overall aim of CorneaRegID is to characterise the precise cell fate map of regenerative LSCs and use this molecular blueprint to instruct transdifferentiation into cells that can match the regenerative potential of LSCs. The hypothesis of CorneaRegID is based on the concept that regenerative LSCs can be induced by the expression of the limbal cell master transcription factor PAX6 and by modulating the epigenetic landscape. Furthermore, we aim to identify genetic modification- and xeno-free conditions for transdifferentiation into LSCs suitable for transplantation through powerful high-throughput screening.

We propose three complementary key objectives:

  • Objective 1: To map the molecular blueprint for transdifferentiation of LSCs;
  • Objective 2: To develop novel transdifferentiation strategies by induced PAX6 expression and modulation of the epigenetic landscape;
  • Objective 3: To perform integrative analysis of transdifferentiated LSCs at the molecular, cellular, and functional levels and generate functional transdifferentiated LSCs that closely resemble cornea-derived transplantable LSCs.
CorneaRegID logo

CorneaRegID brings together three research teams with complementary multidisciplinary expertise: Dr. Zhou (Radboud University) on molecular biology and epigenetics, Dr. Dickman (MUMC+) on corneal disease and LSC transplantation, and Dr. LaPointe (Maastricht University) on regenerative medicine. This work has a broad impact beyond corneal damage, for example, for patients with inherited disorders where both eyes are affected and conditions involving PAX6 deficiency.

Funding

Partners

Radboud University, Maastricht University, Maastricht UMC+

Contact information