Corneal epithelial basement membrane: Structure, function and regeneration
Introduction
Basement membranes (BM) are highly specialized, thin, acellular extracellular matrices underlying cells that separate them from, as well as connect them to, their associated matrix.1 Basement membranes function not only in anchoring adjacent cells and providing scaffolding during embryonic development, but also in migration, differentiation, and maintenance of the differentiated phenotype of associated epithelial, endothelial, or parenchymal cells. In addition, BM control cellular functions by binding and modulating the activation, localization and concentrations of growth factors and cytokines that control the response to corneal injury (Yurchenco, 2011; Torricelli et al., 2013b). BMs also regulate cell polarity, cell adhesion, and migration via their effects on the cytoskeleton of attached cells (Yurchenco, 2011; Torricelli et al., 2013b).
Section snippets
Structure of the corneal epithelial basement membrane
The corneal epithelial BM is positioned between the basal epithelial cells and the stroma. It is first detected at 8–9 weeks of gestation in the human, and after the fourth month of development the corneal epithelium is separated from the stroma by a continuous BM. Evidence has been provided for a stromal cellular origin for some epithelial BM components in the cornea (Hassell et al., 1992; Kabosova et al., 2007; Santhanam et al., 2017). In adult humans, rabbits, mice, and many other species,
Collagens
The presence of collagen type IV was at one time controversial, with some investigators failing in detect type IV collagen in the corneal BM. However, several immunohistochemical studies definitively localized type IV collagen beneath the human corneal epithelium. It appears the disparity between different studies arose as a result of the spatial variability (‘‘horizontal’’ heterogeneity) in the BM composition between the central cornea, limbus, and conjunctiva (Ljubimov et al., 1995). It is
Laminins
Laminins are the most abundant non-collagenous proteins in BM. Laminins are heterotrimeric glycoproteins that are composed of three chains, including one α, one β, and one γ chain. At present, five α, three β, and three γ peptides coded by different genes are known for mice and humans. The trimers were previously designated laminin-1 to −15 in order of their discovery, with no relationship to chain composition. According to the previous nomenclature, a trimer could be identified by either an
Perlecan
Perlecan is the most prevalent HSPG in the EBM. It is a complex, multi-domain protein with several discrete binding partners, including collagen type IV, nidogens and laminins (Kinsella and Wight, 2005). The protein's core consists of five domains that share homology with other molecules involved in nutrient metabolism, cell proliferation, and adhesion, including laminin, the low-density lipoprotein (LDL) receptor, epithelial growth factor (EGF), and the neural cell adhesion molecule (N-CAM) (
The epithelial basement membrane, myofibroblasts and corneal wound healing
Following severe injuries, infection or surgeries of the cornea in which the BM is damaged, large numbers of myofibroblasts are generated and persist in the corneal stroma (Wilson et al., 2017). These fibroblastic cells, and the disorganized extracellular matrix components they secrete, produce fibrosis that alters the structure and function of the corneal stroma and results in a loss of normal transparency (corneal scarring or haze). Studies using chimeric mice transplanted with bone marrow
Proprietary interest statement
The authors don't have any commercial or proprietary interests in this study.
Funding
Supported in part by US Public Health Service grants RO1EY10056 (SEW) and P30-EY025585 from the National Eye Institute, National Institutes of Health, Bethesda, MD, Department of Defense grant VR180066, and Research to Prevent Blindness, New York, NY.
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2022, Experimental and Molecular PathologyCitation Excerpt :We found that perlecan and cellular fibronectin are expressed in the rabbit corneal epithelial basement membrane. By interacting with laminins and collagens, these molecules are thought to function as scaffolds in basement membrane organization (Medeiros et al., 2018; Wilson et al., 2020). Both matrix proteins were tightly associated with the corneal epithelial basement membrane.