Summary: Researchers have identified distinctive genetic features of the glial cells that envelop corneal axons, revealing potential pathways for nerve regeneration and preservation of vision.
Source: University of Connecticut
Researchers at the UConn School of Medicine have uncovered new genetic information about the cells that surround nerve fibers in the cornea. Royce Mohan, a neuroscience professor, and colleagues believe these findings could lead to improved strategies for preserving vision and promoting nerve repair after injury or surgery.
The team focused on the cornea’s glial cells—specifically non-myelinating Schwann cells—that wrap the axons of corneal nerves. Because the cornea must remain transparent to let light reach the retina, it lacks myelin, the insulating material found on many other peripheral nerves. Understanding how corneal Schwann cells function without myelin may reveal molecular targets for enhancing healing and restoring sensation after procedures like corneal transplantation or refractive surgery.
In a study published in the Journal of Neuroscience Research, lead author Paola Bargagna-Mohan, an assistant professor of neuroscience, describes how the team applied single-cell RNA sequencing to catalog every cell type in the cornea and examine gene expression patterns that govern corneal repair and sensory function. The project included collaboration with Paul Robson at The Jackson Laboratory for Genomic Medicine, which provided advanced single-cell biology resources and analytical support.
Bargagna-Mohan and colleagues refined their experimental approach over multiple attempts and received crucial internal funding that allowed them to optimize the workflow and generate robust single-cell data. Their single-cell RNA-seq approach permits fine-grained analysis of gene expression in individual corneal cells, revealing differences not only between cell types but also among cells located in different regions of the cornea.
The cornea’s non-myelinating Schwann cells are uniquely adapted to preserve transparency while supporting nerve function. Mohan notes that these corneal Schwann cells had not previously been isolated and profiled at single-cell resolution. By identifying gene expression signatures specific to corneal Schwann cells, the team has provided new molecular markers and tools that make detailed study possible for the first time.
Their analysis has already revealed genes that appear exclusive to corneal Schwann cells compared with Schwann cells in other tissues. These distinctive genes may help explain how corneal Schwann cells support nerve signaling without producing light-obscuring myelin and could point to mechanisms that protect corneal clarity while permitting sensory transmission.
Mohan’s lab has a grant application under review at the National Eye Institute to expand this research and investigate how these cells contribute to nerve repair and sensory recovery. Better understanding of the molecular programs in corneal Schwann cells could lead to targeted therapies to support healing after corneal transplants, or to reduce persistent sensory symptoms following procedures such as LASIK, where corneal axons and Schwann cells can be injured.
Corneal transplants are common worldwide, yet many recipients do not immediately recover full corneal sensation. Restoring sensory function is important because the cornea’s high sensitivity helps protect the eye from injury. The research team is exploring how Schwann cells survive in preserved donor tissue and whether their survival or function can be enhanced before or after transplantation.
Similarly, patients who undergo laser-assisted in-situ keratomileusis (LASIK) may experience side effects such as burning or gritty sensations. The molecular basis of these symptoms and how to accelerate recovery remain incompletely understood. Characterizing the genes and proteins active in corneal Schwann cells during injury and repair could reveal targets for therapies that reduce discomfort and promote more complete recovery.
Chronic dry eye is another condition where corneal nerve irritation and altered sensory signaling play a role. By identifying which genes are turned on or off in corneal Schwann cells during injury or disease, researchers can prioritize candidates for drug development. For example, topical agents that inhibit harmful proteins or activate protective pathways in Schwann cells may improve wound healing and alleviate chronic corneal pain.
About this neuroscience research news
Source: University of Connecticut
Contact: Press Office – University of Connecticut
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Original Research: Closed access. “Corneal nonmyelinating Schwann cells illuminated by single‐cell transcriptomics and visualized by protein biomarkers” by Bargagna-Mohan et al., Journal of Neuroscience Research
Abstract
Corneal nonmyelinating Schwann cells illuminated by single‐cell transcriptomics and visualized by protein biomarkers
The cornea is among the most densely innervated tissues in the human body. As peripheral nerves enter the corneal stroma, their axons lose myelin and continue into the central cornea ensheathed only by nonmyelinating corneal Schwann cells (nm‑cSCs). This arrangement is thought to be critical for maintaining clear vision. Using single‑cell RNA sequencing (scRNA‑seq), microscopy, and transgenic reporter models, the authors characterized nm‑cSCs from the central cornea. Computational analyses including principal component analysis, uniform manifold approximation and projection (UMAP), and unsupervised hierarchical clustering of scRNA‑seq data from central corneal cells of male rabbits revealed distinct clusters corresponding to known corneal cell types and a unique cluster representing nm‑cSCs. To validate protein expression of candidate genes, cross‑species immunostaining of mouse corneal whole mounts followed by confocal microscopy confirmed the presence of several representative nm‑cSC proteins. The proteolipid protein 1 (PLP1) gene was expressed in nm‑cSCs, and the Plp1‑eGFP transgenic mouse line enabled specific visualization of corneal Schwann cells in adult animals. Among putative cornea‑specific Schwann cell genes, Dickkopf‑related protein 1 (DKK1) was found in nm‑cSCs. These results provide new molecular markers and experimental tools for studying nm‑cSCs in tissue and in vivo, and they establish a foundation for future work on nerve repair and corneal sensory function.