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Regenerative Synergy: Corneal Nerves, Mesenchymal Cells, and Limbal Stem Cells in Epithelial Renewal
Arif Hussain MD1*, Chilando Mulenga BS1, Jordan Crabtree BS1, Konstantin Feinberg PhD1 and Gregory Borschel MD1
1 Division of Plastic Surgery, Department of Surgery, Indiana University School of Medicine, Indiana
2025-01-10
Presenter: Arif Hussain
Affidavit:
Gregory H. Borschel, MD
Director Name: Gregory H. Borschel
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial
Introduction:
Corneal innervation is essential for corneal epithelial renewal. Neurotrophic keratopathy (NK), a condition resulting from the loss of corneal innervation, can lead to blindness. The corneal limbus hosts Limbal Stem Cells (LSCs), Mesenchymal Limbal Niche Cells (MLNCs), and Schwann Cells (SCs), with corneal sensory nerves regulating their activities to support epithelial regeneration.
Objectives:
1. Investigate how MLNCs interact with LSCs during corneal epithelial renewal.
2. Explore the role of corneal sensory nerves in regulating these interactions.
Methods:
We utilized a rodent NK model to assess the impact of corneal denervation on epithelial healing. Single-cell RNA sequencing provided a detailed analysis of the cellular composition in the limbal niche. Using transgenic mice expressing markers specific to LSCs, MLNCs, and SCs, we achieved dynamic, in vivo visualization of these cells.
To further understand cellular communication, we developed a transcriptome-based model predicting the paracrine signaling network among these cell types. Future studies will implement denervation and neurotization procedures in the NK model to monitor MLNC and LSC responses to neural manipulations. Additionally, we will investigate the effects of genetic ablation of MLNCs on LSC activity and corneal epithelial healing.
Conclusions:
Corneal innervation is crucial for epithelial recovery after injury, with LSCs and MLNCs as key players in the limbal niche. These cells engage in a complex paracrine signaling network essential for regeneration. Future research will focus on elucidating the specific role of corneal nerves in modulating MLNC-LSC interactions during epithelial renewal, advancing our understanding of neurotrophic support in corneal repair.
