A Protein Necessary for Corneal Healing

Stem cells in the area cannot properly repair tisssue without it.


Long-tailed macaque faceLong-tailed macaque face

Researchers have discovered a protein that is necessary for proper healing of damaged corneal tissue and that this protein decreases with age.

Repairing a shield that is easy to damage

The corneal epithelium covers the cornea, which focuses light onto the retina of the eye. Although it fulfills multiple protective functions, this tissue is not particularly thick and is susceptible to damage [1]. Therefore, it is regularly renewed by limbal stem cells (LSCs), a population of stem cells deep in the cornea [2].

However, alongside a long list of other negative changes, the niche of these cells diminishes with aging [3]. If these cells cannot go to a damaged area and properly heal it in time, keratocytes will appear in the area and cause scarring [4].

Because the eyes of humans and smaller mammals are somewhat different, eye experiments often need to be performed in animals that are evolutionarily closer to us. Therefore, alongside human corneal tissue donations and mice, these researchers used long-tailed macaques, non-human primates that are frequently used for these sorts of experiments.

A single gene and protein

In their first experiment, the researchers scraped half of the corneal epithelium of one eye of both young and elderly macaques, then observed their healing. Within three days, the younger group was well on its way to healing, while the older group was not. By day six, the younger group had completely healed, but older monkeys took twice as much time. Unlike the younger monkeys, the older monkeys had fibroblasts in the area along with increased corneal opacity after the injury, demonstrating imperfect healing with scar tissue. These results were also found to be true in mice.


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RNA transcription in younger and older LSCs was similar in uninjured tissue. However, after injury, they reacted significantly differently, with expressions related to repair and proliferation being far more upregulated in younger tissue. One of these genes coded for the SECTM1 protein, which had considerably greater expression in young corneas after wounding.

Encouraged by this discovery, the researchers then tested the effects of SECTM1 on LSCs. LSCs unable to express SECTM1 were greatly restricted in proliferation, although it did not affect their fundamental nature as stem cells. Applying extra SECTM1 to LSCs encouraged their proliferation, with greater doses having more effect. This was found to affect downstream genes, notably CDCA7, which is a critical part of the cell cycle.

The researchers then returned to animal experiments. Mice that were given anti-SECTM1 treatment experienced delayed corneal repair, while giving SECTM1 to older mice and macaques dramatically sped up their repair. In mice, it was found to make the corneas less opaque after healing was complete.

Notably, this treatment is a topical solution that could, in theory, be used in eyedrops or creams. However, the mechanism of action and potential side effects are not yet completely understood, and further studies will need to be performed before this could be clinically available for patients.

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[1] Bashir, H., Seykora, J. T., & Lee, V. (2017). Invisible shield: review of the corneal epithelium as a barrier to UV radiation, pathogens, and other environmental stimuli. Journal of ophthalmic & vision research, 12(3), 305.


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[2] Gonzalez, G., Sasamoto, Y., Ksander, B. R., Frank, M. H., & Frank, N. Y. (2018). Limbal stem cells: identity, developmental origin, and therapeutic potential. Wiley Interdisciplinary Reviews: Developmental Biology, 7(2), e303.

[3] Notara, M., Shortt, A. J., O’Callaghan, A. R., & Daniels, J. T. (2013). The impact of age on the physical and cellular properties of the human limbal stem cell niche. Age, 35, 289-300.

[4] Shu, D. Y., & Lovicu, F. J. (2017). Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis. Progress in retinal and eye research, 60, 44-65.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.