Histology and Biochemistry

The cornea consists of three different cellular layers and two interfaces: the epithelium, Bowman's layer, the stroma, Descemet's membrane, and the endothelium (see Fig. 1.1).^[55] The cell types that constitute the cornea thus include epithelial cells, keratocytes (corneal fibroblasts), and endothelial cells. Components of the cornea interact with each other to maintain the integrity and function of the tissue, with the precise arrangement of the various components contributing to its transparency and strength.

Corneal epithelium

The corneal and conjunctival epithelia are continuous and together form the ocular surface. They are both composed of nonkeratinized, stratified, squamous epithelial cells. Although their characteristics differ, both corneal and conjunctival epithelia cooperate to provide the biodefense system of the anterior surface of the eye.^[56],[57] The thickness of the corneal epithelium is approximately 50 µm, which is about 10% of the total thickness of the cornea (see Fig. 1.1), and it is constant over the entire corneal surface.

The corneal epithelium consists of five or six layers of three different types of epithelial cells: superficial cells, wing cells, and columnar basal cells, the latter of which adhere to the basement membrane adjacent to Bowman's layer (Fig. 1.4). Only the basal cells of the corneal epithelium proliferate. The daughter cells differentiate into wing cells and subsequently into superficial cells, gradually emerging at the corneal surface. The differentiation process requires about 7 to 14 days, after which the superficial cells are desquamated into the tear film.^[58] Ultraviolet radiation, hypoxia, or mechanical stress induces apoptosis (programmed cell death) and desquamation of corneal epithelial cells.^[59–62]

An important physiological role of the corneal epithelium is to provide a barrier to external stimuli. The presence of junctional complexes between adjacent corneal epithelial cells prevents the passage of such agents into the deeper layers of the cornea. Both cell–cell and cell–matrix interactions are important for maintenance of the normal stratified structure and physiological functions of the corneal epithelium. The characteristics of the different types of intercellular junctional complexes present in the corneal epithelium are summarized in Table 1.2 and in Figures 1.4, 1.5, and 1.6.Tight junctions (zonula occludens) are present mostly between cells of the superficial cell layers and provide a highly effective barrier to prevent the penetration of tear fluid and its chemical constituents. Hemidesmosomes (zonula adherens) and desmosomes are present in all layers of the corneal epithelium, whereas gap junctions, which allow the passage of small molecules between cells, are present in the wing cells and basal cells. After damage to the corneal epithelium, actively migrating epithelial cells no longer manifest gap junctions or desmosomes in the wounded region lacking a basement membrane. Reestablishment of the continuity of the corneal epithelium is accompanied by the synthesis and deposition of basement membrane proteins and by the reassembly of the various types of junctional apparatus, suggesting that the presence of the basement membrane may be required for re-formation of cell–cell junctions in the corneal epithelium (Fig. 1.6).^[63]

Flat | | | |

Microvilli | | | |

Microplicae | | 2–4 |

40–60 µm in diameter | | | |

4–6 µm thick at the nucleus | | | |

2 µm thick at the periphery | | − | Entire surface |

Desmosomes | | | |

Tight junctional complexes | | | |

(zonula occludens) | | Sparse | + | + | ? |

Desmosomes | | | |

Gap junctions | | Sparse | +++ | + | +/− |

18–20 µm high | | | |

8–10 µm in diameter | | | |

Flat at posterior surface | | + | Apical surface |

Desmosomes | | | |

Gap junctions | | | |

Hemidesmosomes | |

More than superficial cells | | | |

Large numbers of glycogen granules | | | |

Prominent mitochondria and Golgi apparatus | | +++ | + | + |

In corneal epithelial cells, intermediate filaments of the cytoskeleton are formed by specific types of acidic (type I) and basic (type II) keratin molecules. Basal cells of the corneal epithelium express keratin 5/14, like basal epidermal cells of the skin. However, keratin 3/12 (64-kDa keratin) is specifically expressed in the epithelium of the cornea, not being found in that of the conjunctiva or in the epidermis.^[64],[65] Genetic mutation of the keratin 12 gene is responsible for Meesmann's dystrophy of the corneal epithelium.^[66]

Replacement of most organs or tissues by transplantation from a genetically nonidentical individual is associated with an immune response that may lead to rejection. In contrast, the cornea is ‘immune privileged,’ a characteristic that is critical for the success of corneal transplantation. Dendritic Langerhans cells, specialized macrophages derived from the bone marrow that are implicated in antigen processing, are abundant at the periphery of the corneal epithelium but are not present in the central region of the normal cornea.^[67],[68] These cells express human leukocyte antigen (HLA) class II molecules and are thought to function in the afferent arm of the ocular immune response by presenting antigens to T lymphocytes.^[69],[70] Injury to the central cornea results in the rapid migration of peripheral Langerhans cells to the damaged area.

Superficial cells

The surface of the corneal epithelium contains two to three layers of terminally differentiated superficial cells. In contrast to the epidermis of the skin, the corneal epithelium is not normally keratinized, although it may become so under pathological conditions such as vitamin A deficiency. These cells are flat and polygonal with a diameter of 40–60 µm and a thickness of 2–6 µm (see Table 1.2). Their surface is covered with microvilli.^[71] Given that superficial cells are well differentiated, they do not proliferate.