Introduction:
A single layer of cells present on the inner surface of the cornea is called corneal endothelium. These cells are present at the cornea's posterior surface facing the eye's anterior chamber. These specialized, flattened mitochondria-rich cells are important to maintain the cornea's transparency. The normal structure of these cells is affected by various factors like aging, systemic disorders, and genetic disorders. As a result, assessing corneal endothelial health is important for identifying underlying conditions.
Why Is It Important?
William Bowman first described the corneal endothelium cells in the mid-19th century. These cells are derived from the neural crest (an embryonic structure that forms tissues) during embryonic development. During birth, the endothelium cell density is 6000 cells per square millimeter. But gradually, the number of cells in the epithelium decreases with age. By the age of 85, approximately 2300 cells/square millimeters are only present. The rate of decrease of the cells is 0.6% per year. Maintaining a healthy structure is important for good ocular health, as these cells never divide.
The corneal endothelium maintains hydration and the movement of nutrients and molecules. The corneal endothelium has three functions.
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When corneal endothelium is healthy, and a sufficient number of cells are present, it acts as a barrier. It prevents the bulk flow of the fluid from aqueous humor (clear liquid in the front part of the eye) to the corneal stroma (thick layer of the cornea). Only selective molecules and nutrients can pass the barrier.
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Cells of the corneal endothelium (single layers of cells in the cornea) are rich in mitochondria and transport proteins. These two factors are essential for creating osmotic gradients. With the help of transport proteins, the osmotic gradient helps move various ions. This mechanism is known as a pump-leak mechanism.
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Corneal endothelium also secretes extracellular proteins that form collagen fibers. This helps to form Descemet's membrane.
Any abnormality of the cellular function of corneal endothelium or reduction in the number of cells disrupts these functions. Disrupting the corneal endothelium's function leads to visual acuity problems and altered intraocular pressure.
What Are Corneal Diseases?
The diseases responsible for changes in the normal form and function of the corneal epithelium can be of two types:
1. Primary Corneal Endotheliopathy:
These are the inflammatory conditions that disrupt the normal functioning of the corneal endothelium. They can be of four types.
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Fuchs' Endothelial Corneal Dystrophy: The condition is a slow progressive inherited bilateral disorder. This disease mainly affects during the fifth or sixth decades of life. The exact etiology responsible for this condition is not known. Still, epigenetic changes (changes in cellular function at the molecular level) or mutation of certain genes like COL8A2 might be the causative factor. In this condition, the number of endothelial cells decreases, but cellular size increases. The cells secrete an excess amount of collagen, and the barrier function of the cells is lost; as a result, the following things can be seen.
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Corneal Edema: Cells cannot maintain fluid balance, resulting in swelling of the cornea and loss of transparency.
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Guttate Cornea: The enlarged endothelium appears as drop-like warts projected from Descemet's membrane's posterior surface.
2. Posterior Polymorphous Dystrophy: This autosomal dominant disorder affects both eyes. It is also known as Schlichting dystrophy. The mutation of several genes like OVOL2 and COL8A2 causes this. The clinical features are:
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Gray-white plaques or broad bands with serrated edges on the endothelium.
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Presence of clustered vesicles.
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Epithelial-like abnormal cell infiltration is seen in the isolated areas of the endothelium.
3. Congenital Hereditary Endothelial Dystrophy: This autosomal recessive disorder affects both eyes and is associated with the mutation of the SLC4A11 gene. Affected persons suffer from clouding of vision and nystagmus (rapid involuntary eye movement). The clinical manifestations are:
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Thickened and laminated Descemet's membrane.
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Degeneration of the endothelial cells.
4. Iridocorneal Endothelial (Ice) Syndrome: This is an acquired disorder of three syndromes: iris atrophy, Chandler's syndrome (associated with proliferation of corneal epithelium), and Cogan–Reese iris nevus syndrome (presence of nodules in the iris). This syndrome usually affects one eye but sometimes may affect both eyes also. This syndrome typically affects adults (more often women in the third to fifth decades of life). The clinical manifestations are:
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Beaten metal or cobblestone appearance of the endothelium.
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Affected endothelium cell shows pleomorphism and polymegethism (alteration in the normal form and function of the cells).
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Loss of normal cell junction.
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Abnormal cells present on the periphery of the iris form a membrane that gradually displaces the iris.
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Secondary Corneal Endotheliopathy:
In this type, the corneal endothelium cells are affected indirectly by some other disorder or systemic conditions or may be affected by trauma.
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Contact Lens Wear:
One of the common causes of corneal endothelium trauma is contact lenses. Due to repeated trauma, the normal hexagonal shape of the cell is lost. The cells show a large number of variations in form and function. This can be attributed to the excessive use of lenses which leads to hypoxia (decrease in oxygen level).
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Age-Related Changes:
As discussed earlier, the number of corneal endothelial cells decreases with age. A minimum of 2000 cells/square millimeters is required to maintain normal form and function. The normal gap and tight junction between the cells are also lost. As a result, the normal permeability is lost, and fluid accumulation occurs. This leads to corneal edema and loss of transparency. Ultimately separation of the corneal epithelium from its underlying matrix occurs, and small blister-like elevations known as bullae are formed.
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Surgical Injury:
The rapid loss of corneal endothelial cell count is observed after cataract surgery. The loss may be caused by surgical trauma during the procedure or maybe a lack of supply of nutrition from aqueous humor post-surgically.
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Glaucoma:
These are a group of eye conditions that damage the optic nerve. Glaucoma is associated with increased intraocular pressure. This pressure alters the osmotic gradient, and the gap and the tight junction between the endothelial cells are lost.
How to Treat Corneal Disorders?
The main treatment option for the loss of corneal endothelium is corneal decompression (reduction of pressure), along with keratoplasty. Corneal decompression helps to maintain pressure gradient and reduces corneal edema. Keratoplasty is a procedure in which corneal tissues are taken from the donor site and implanted into the patient's eye.
Conclusion:
The corneal endothelium maintains the natural form and function of the cornea. Endothelial cells maintain the integrity and permeability of the cornea. Several genetic disorders and systemic conditions affect the natural health and number of corneal endothelial cells. Modern treatment procedures like corneal transplantations and cell therapy can help regenerate corneal health.
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