Mechanism of Corneal Repair and Regeneration in the Human Eye

Introduction

Cornea, also called the window of infection of the eyes, is the outermost transparent part of the eye. Corneal damage is common from dust particles, foreign bodies, or eye infections. Corneal epithelium with high regenerative capacity helps in proper wound healing. The damaged cornea is replaced with healthy transplants or treated with techniques that utilize the regenerative potential of the cornea.

What Is the Cornea?

The cornea is the transparent part of the eye in the front portion, covering the iris and pupil. The colored part of the eye is called the iris, and the pupil is the opening at the center of the eye. The cornea helps focus most of the light that enters the eye. Cornea appears as a smooth, transparent lens that is very strong and durable. The cornea has a strength of about 200 collagen lamellae, which results in the high mechanical strength of the cornea. Cornea lacks blood supply, making it more susceptible to infections.

What Are the Functions of the Cornea?

• Protective Function- The cornea acts as a shield and protects the rest of the eye from dust germs and other harmful matters.

• Focusing Element of the Eye - The cornea is the outermost lens that acts as a window, allowing light rays to enter and focus on the eye. Cornea provides 75 % of the focusing power of the eye.

• Function as a Filter - Cornea helps in screening out harmful ultraviolet rays that are highly susceptible to injury to the eye.

• Regenerative Function - Corneal epithelium is the only part of the cornea that undergoes maintenance and regeneration following an injury.

What Is a Corneal Injury?

A corneal injury is a wound caused to the cornea of the eye. Eye injuries can be

• Abrasion-like scratches on the corneal surface.

• Chemical injuries from harmful fluids that enter the eye.

• Contact lens problems from overuse poor fit or sensitivity to the contact lens.

• Foreign bodies that end us in the eye like sand or dust can cause corneal injury.

• Harmful UV rays entering the eye can cause corneal injury.

What Is a Corneal Repair?

Corneal repair is a procedure that aims to restore a normal, healthy cornea. The diseases affecting the cornea can cause severe visual impairments. The traditional use of eye medicines increased the thickness of corneal ulceration. A new method of corneal transplant was done with very few complications and a high success rate. This method utilized the body's own repair mechanisms to heal the injured cornea.

• Keratoplasty - Keratoplasty is a corneal transplant method used to replace a damaged cornea with healthy transparent tissue from a donor. The three types of keratoplastic procedures are
  • Penetrating Keratoplasty - Surgical procedure where the entire cornea is replaced with the donor tissue.
  • Lamellar Keratoplasty - In this procedure, only damaged layers are replaced with the donor tissue leaving the healthy part of the cornea intact.
  • Endothelial Keratoplasty - Keratoplasty procedure that replaces deeper layers of the cornea.

• Corneal Immune Privilege - Eyes have a special feature of the immune system called immune privilege. The immune system of the eye limits the local immune and inflammatory responses associated with an injury. The immune privilege is mediated by local and systemic mechanisms. Due to this added benefit, the foreign tissue grafts placed in the eye are not rejected.

• Inhibiting Angiogenesis - Avascularity or lack of blood vessels in the cornea is important to provide clear vision. Angiogenesis is the process of new blood vessel formation and this process is blocked in the cornea to ensure avascularity. But following an injury, wound healing takes place in the cornea similar to any other wound healing. So there will be an increased production of pro-angiogenic factors during wound healing. This is regarded as an undesirable event and adequate measures are taken to stop the growth of blood vessels into the cornea.

• Blocking Immune Signaling Pathway- Aggressive inflammatory response following an eye injury can damage the re-epithelialization process of the cornea. The immune signaling pathways are blocked reducing the inflammatory response.

• DSAEK Procedure - Descemet stripping automated endothelial keratoplasty is a surgical procedure to fix diseased or damaged cornea. It is a partial-thickness cornea transplant, where the transplanted tissue is approximately 100 to 200 microns thick. The surgical procedure is designed to avoid contact with donor epithelium. This procedure is done to treat corneal edema and endothelial dystrophy.

  • Corneal Edema - Also known as the swelling of the cornea due to the accumulation of fluid.

  • Endothelial Dystrophy - It is a clinical condition characterized by the loss of endothelial cells

• Advantages include rapid healing time, visual rehabilitation, and less risk for complications like graft rejection and suture-associated complications. Also good postoperative changes in visual acuity.

What Is Corneal Regeneration?

Following an eye injury, only the corneal epithelial cells undergo regeneration. Damage to the cornea can result in loss of vision and severe eye pain. The regenerative process helps to heal the injury and provide a clearer and brighter vision.

A clear cornea will bring clear vision. The epithelial cells of the cornea, which have a regenerative capacity, constantly renew themselves to maintain the uniformity of the refractive surface. Cells present at the corneal surface are replaced with new forms of cells. The new cells are formed from stem cells located at the edge of the cornea, called the 'limbus." The region of the process will be interrupted in a person with a damaged limbus. The loss of stem cells is called limbal stem cell deficiency (LSCD). This condition allows the growth of conjunctiva over the cornea, causing pain and severe conditions that result in blindness.

What Are the Treatment Methods for Corneal Regeneration?

• Limbal Transplantation:

In limbal stem cell deficiency, limbal transplantation is used to achieve the surface reconstruction of the cornea. This procedure requests a large limbal graft from the other healthy eye or another donor. This procedure can be done in patients with unilateral or bilateral limbal stem cell deficiency.

The drawbacks associated with this procedure are post-operative complications. It includes

• • Graft Rejection - Cells or tissues transplanted from a host may recognize it as a foreign body and produce an immune response against the tissue. This results in the rejection of graft by the body called graft rejection.
  • Bacterial or Fungal Keratitis - It is a pathological condition of the cornea causing inflammation, corneal edema, and associated vision problems.
  • Organ Dysfunction - Long-term immunosuppression is done before the surgery resulting in a high risk of eye infections and liver and kidney dysfunction.

• Tissue Engineering

This technology combined the principles of engineering and life sciences to create a biological substitute for human cells that restore and improve tissue functioning. The tissue engineering procedures make analogous human cornea that is used as a corneal tissue substitute. The tissue-engineered cornea is made with suitable biomaterials for an increased success rate.

Conclusion

Cornea plays an important role in proper vision. The cornea allows the entry of light rays into the eyes. Injuries occurring to a cornea can be corrected by the regenerative capacity of corneal cells. Corneal damage can be corrected by a corneal transplant or other regenerative procedures like limbus transplantation or tissue engineering. More studies and trials are needed for the proper application of tissue engineering techniques for corneal implantation. Successful clinical trials in tissue engineering processes can be a boon in corneal repair.