The stroma constitutes approximately 90% of the total corneal thickness in humans (see Fig 2-2). It is composed of collagen-producing keratocytes, ground substance, and collagen lamellae. The collagen fibrils form obliquely oriented lamellae in the anterior third of the stroma (with some interlacing) and perpendicular lamellae in the less compact posterior two-thirds (see Chapter 8, Fig 8-3).
The corneal collagen fibrils extend across the entire diameter of the cornea, finally winding circumferentially around the limbus. The fibrils are remarkably uniform in size and separation, and this regularity helps determine the transparency of the cornea (see also Chapter 8). Separation of the collagen fibrils by edema leads to stromal clouding. The stroma’s collagen types are I (predominant), III, IV, V, VI, XII, and XIV. Type VII forms the anchoring fibril of the epithelium. Natural crosslinking occurs with aging.
The ground substance of the cornea consists of proteoglycans that run along and between the collagen fibrils. Their glycosaminoglycan components (eg, keratan sulfate) are negatively charged and tend to repel each other—as well as draw in sodium and, secondarily, water—producing the swelling pressure of the stroma. The keratocytes lie between the corneal lamellae and synthesize both collagen and proteoglycans. Ultrastructurally, they resemble fibrocytes.
The cornea has approximately 2.4 million keratocytes, which occupy about 5% of the stromal volume; the density is higher anteriorly (1058 cells/mm2) than posteriorly (771 cells/mm2). Keratocytes are highly active cells rich in mitochondria, rough endoplasmic reticula, and Golgi apparatus. They have attachment structures, communicate through gap junctions, and have unusual fenestrations in their plasma membranes. Their flat profile and even distribution in the coronal plane ensure a minimum disturbance of light transmission.
Müller LJ, Pels L, Vrensen GF. Novel aspects of the ultrastructural organization of human corneal keratocytes. Invest Ophthalmol Vis Sci. 1995;36(13):2557–2567.
Mustonen RK, McDonald MB, Srivannaboon S, Tan AL, Doubrava MW, Kim CK. Normal human corneal cell populations evaluated by in vivo scanning slit confocal microscopy. Cornea. 1998;17(5):485–492.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.