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Insulin Beyond Diabetes: Healing Epithelial Defects

Vision Science Academy

Avantika Bind, B. Optom.

M. Optom Student, The Sankara Nethralaya Academy, Chennai, India

 
The cornea and conjunctiva form the outer surface of the eye, protected by a tear film from environmental factors. The transparent cornea, which lacks blood vessels, acts as a barrier and contributes to about 75% to the eye’s focusing ability. Its epithelium, made of non-keratinised stratified squamous cells with tight junctions, protects the eye and provides a smooth surface for vision, regenerating every 7-10 days through limbal stem cell differentiation. (1-3)

Figure 1: Layers of the cornea

Persistent Epithelial Defects: Causes and Conventional Treatments

A healthy epithelium is essential for protecting the eye from infection and preventing damage to underlying tissues. Acute epithelial defects in a healthy cornea typically heal within 7-14 days. (4,5) Persistent epithelial defects (PEDs) occur when epithelialisation fails, causing discomfort, vision issues, and potential disruption due to adhesion problems, stem cell deficiency, trauma, medications, or infections. (6)

Treatment for PEDs typically starts with conservative methods such as preservative-free lubricating eye drops, bandage contact lenses, and punctal plugs. (7) If these are ineffective, options include autologous serum eye drops and surgical procedures like debridement and amniotic membrane grafts, with autologous serum and platelet-rich plasma drops as second-line treatments. (8-10) If these fail, more aggressive options like amniotic membrane transplantation or surgery may be necessary. Emerging treatments, such as recombinant nerve growth factor and epidermal growth factor, provide non-invasive alternatives, while corneal neurotisation shows promise in restoring sensation and enhancing healing. (11,12)

Emerging Role of Insulin in Corneal Healing

Insulin-like Growth Factors (IGFs) are crucial for the growth and proliferation of corneal epithelial cells through insulin and IGF receptors. (13,14) Insulin promotes the migration of human epidermal keratinocytes and supports wound healing. It is present on the corneal surface and in the tear film, enhancing epithelial cell growth and potentially aiding in resistant epithelial defects. (15-17)

Topical insulin is safe for ocular use in humans and shows promise for treating Persistent Epithelial Defects. (18-20) Insulin, a peptide closely related to Insulin-like Growth Factor (IGF), stimulates keratinocyte migration and plays a role in wound healing. (16,21) The importance of glucose for corneal cell functionality is known, with glucose uptake occurring independently of insulin via the active glucose transporter GLUT1, which increases after wounding to support cell migration and proliferation. (22,23)

The mechanism by which insulin aids epithelialisation is still unclear. However, in diabetic animals, topical insulin has been shown to normalise DNA synthesis in basal epithelial cells within 48 hours post-wound, suggesting a role in cell proliferation for re-epithelialisation. Additionally, insulin may help regulate receptor homeostasis in corneal epithelial cells. (13)

A study concluded that topical insulin 1 unit, four times daily, improved corneal epithelial healing in diabetic patients post-vitrectomy, with no adverse events. (24) It was found that topical insulin eye drops (100 units/mL, twice daily) caused no ocular side effects in healthy individuals, and no systemic absorption was observed; the drops were as comfortable and clinically harmless as sterile saline. (25,26)

Conclusion

Topical insulin is safe for ocular use and effectively stimulates corneal re-epithelisation in persistent PEDs. By promoting cell growth, reducing inflammation, and aiding tissue repair, it provides a valuable strategy for managing challenging cases. Its therapeutic potential in epithelial healing is gaining recognition.

References

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