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Mechanisms Governing Nerve-mediated Control Of Corneal Epithelial Renewal: A New Hope For Patients With Neurotrophic Keratopathy
Arif Hussain, MD1, Kaveh Mirmoeini, MD2, Chilando M. Mulenga, B.S1, Jordan Crabtree, B.S1, Kiana Tajdaran, MD2, Konstantin Feinberg, PhD1, Gregory Borschel, MD1.
Indiana University School of Medicine
2025-01-09
Presenter: Chilando M Mulenga
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting
Director Name: William Wooden, MD
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background:
Corneal clarity, essential for vision, is maintained by limbal stem cells (LSCs), which generate transparent limbal epithelial cells. Beyond their protective function, corneal sensory nerves are believed to stimulate LSC activity through mechanisms that remain unclear. Neurotrophic keratopathy (NK) caused by absent corneal innervation from congenital underdevelopment or acquired etiologies (e.g., tumors, trauma, infections, ocular surgery) leads to corneal ulceration and eventual blindness. Corneal nerve-associated Schwann cells (SCs) play a crucial role in wound healing and epithelial maintenance. Our scRNA-seq studies indicate that several trophic factors secreted by SCs regulate the activity of LSCs. We identified pleiotrophin (PTN) as a novel SC-derived regulator of corneal renewal.We hypothesize that PTN is involved in the regulation of LSC activity and, thereby, plays a critical role in mediating corneal epithelial renewal, particularly when co-administered with CNTF (ciliary neurotrophic factor).
Methods: In our two NK models, either local ablation of SC or surgical corneal denervation causes corneal ulceration and prevents healing of experimental corneal ulcers. To define the role of PTN in corneal epithelial renewal, we tested the effects of topical recombinant PTN alone or with other trophic factors on the healing of surgically denervated or genetically SC-ablated deepithelialized rodent corneas.
Results: (i) PTN alone induced rapid healing, and, (ii) when applied together with (CNTF), induced complete recovery of corneal clarity.
Conclusions: Under conditions of denervation or SC loss, exogenous PTN with CNTF rescue corneal epithelial renewal. These findings will be leveraged towards the development of topical treatments for NK.
