Stroma

The stroma makes up approximately 90% of the total corneal thickness. Stromal cells, known as keratocytes, constitute 10%–40% of corneal volume, depending on age; loss of keratocyte density occurs with age. Usually, these cells reside between the collagen lamellae. The stroma is made up of roughly 200 lamellae, which are 1.5–2.5 μm thick and composed of collagen fibrils enmeshed in a matrix consisting of proteoglycans, proteins, and glycoproteins. The stromal fibrils within each lamella are narrow and uniform in diameter; in humans, the average fibril diameter is 30 nm. The stroma is less compact posteriorly, facilitating a deeper placement of intrastromal ring segments for keratoconus.

Collagen fibrils within each lamella run parallel to one another from limbus to limbus. The orientation of the lamellae with each other depends on the location within the stroma. The lamellae are obliquely oriented in the anterior third and perpendicular in the posterior two-thirds of the stroma (Fig 8-3). Also, collagen fibrils in each lamella are regularly spaced, with a center-to-center distance of 55–60 nm. The narrow and uniform diameter of collagen fibrils and their regular arrangement are characteristic of collagen of the corneal stroma and are necessary for the transparency of this tissue (Fig 8-4).

Type I is the major collagen component of the corneal stroma; it constitutes approximately 70% of the total stromal dry weight. Immunohistochemical and biochemical studies have demonstrated that normal adult corneal stroma also contains collagen types V, VI, VII, XII, and XIV. Type III collagen production is associated uniquely with stromal wound healing.

After collagen, proteoglycans are the second most abundant biological constituents of the cornea; they constitute approximately 10% of the dry weight of the cornea. Proteoglycans are the constituents that confer hydrophilic properties to the stroma. They are glycosylated proteins with at least 1 glycosaminoglycan (GAG) chain covalently bound to the protein core. GAGs are composed of repeating disaccharides. The GAGs found in corneal stroma include

• keratan sulfate

• chondroitin sulfate

• dermatan sulfate

Figure 8-3 Orientation of stromal collagen fiber lamellae. The anterior stroma is more compact than the posterior stroma, particularly at the Bowman layer.

(Modified with permission from Levin LA, Nilsson SFE, Ver Hoeve J, Wu SM. Adler’s Physiology of the Eye. 11th ed. Philadelphia: Elsevier/Saunders; 2011:107.)

Regulation of spacing between the stromal collagen fibrils is thought to result from highly specific interactions between the proteoglycans and the collagen fibrils. When these interactions are disturbed, the ability of the cornea to remain transparent is profoundly affected.

Matrix metalloproteinases (MMPs) are a family of Zn²⁺-dependent enzymes responsible for degradation of the components of the extracellular matrix (including proteoglycans and various types of collagens) during normal development as well as in disease processes. Of the more than a dozen known metalloproteinases, only MMP-2 proenzyme has been found in the normal healthy cornea. However, after corneal injury, additional MMPs (including MMP-1, MMP-3, and MMP-9) are synthesized. The proteinase inhibitors of the cornea play a key role in corneal protection by restricting damage during corneal inflammation, ulceration, and wound healing. Many of these inhibitors are synthesized by resident cells of the cornea; some are derived from tears, aqueous humor, and limbal blood vessels.

• Randleman JB, Dawson DG, Grossniklaus HE, McCarey BE, Edelhauser HF. Depthdependent cohesive tensile strength in human donor corneas: implications for refractive surgery. J Refract Surg. 2008;24(1):S85–S89.

Figure 8-4 Cornea and sclera. A, Both are composed of similar collagen fibrils. However, fibril diameter and fiber density are consistent throughout the cornea, whereas in the sclera, they are not. B, The density of the fibers decreases in the sclera (blue), and the variation in fibril diameter increases (red). This heterogeneity contributes to the opacity of the sclera, as compared with the cornea, despite their similar collagen fiber composition.

(Modified with permission from Levin LA, Nilsson SFE, Ver Hoeve J, Wu SM. Adler’s Physiology of the Eye. 11th ed. Philadelphia: Elsevier/Saunders; 2011:117.)

Figure 8-5 Thickening of the Descemet membrane with age as the posterior nonbanded layer is continuously produced.

(Courtesy of John Marshall.)

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.