Abstract
Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva with frequent involvement of the corneal limbus. Its pathogenesis has been mainly attributed to sun exposure to ultraviolet-B radiation. Obtained evidence has shown that it is a complex and multifactorial process which involves multiple mechanisms such as oxidative stress, dysregulation of cell cycle checkpoints, induction of inflammatory mediators and growth factors, angiogenic stimulation, extracellular matrix (ECM) disorders, and, most likely, viruses and hereditary changes. In this review, we aim to collect all authors’ experiences and our own, with respect to the study of fibroelastic ECM of pterygium. Collagen and elastin are intrinsic indicators of physiological and pathological states. Here, we focus on an in-depth analysis of collagen (types I and III), as well as the main constituents of elastic fibers (tropoelastin (TE), fibrillins (FBNs), and fibulins (FBLNs)) and the enzymes (lysyl oxidases (LOXs)) that carry out their assembly or crosslinking. All the studies established that changes in the fibroelastic ECM occur in pterygium, based on the following facts: An increase in the synthesis and deposition of an immature form of collagen type III, which showed the process of tissue remodeling. An increase in protein levels in most of the constituents necessary for the development of elastic fibers, except FBLN4, whose biological roles are critical in the binding of the enzyme LOX, as well as FBN1 for the development of stable elastin. There was gene overexpression of TE, FBN1, FBLN5, and LOXL1, while the expression of LOX and FBLN2 and -4 remained stable. In conclusion, collagen and elastin, as well as several constituents involved in elastic fiber assembly are overexpressed in human pterygium, thus, supporting the hypothesis that there is dysregulation in the synthesis and crosslinking of the fibroelastic component, constituting an important pathogenetic mechanism for the development of the disease.
Highlights
Due to the scarcity of studies related to the latter mechanism implicated in the development of pterygium pathology, in this study, we focus on extracellular matrix (ECM) disorders and review the most studied ECM constituents, with a special emphasis on updating and summarizing the main findings obtained by our research group, whose members have many years of experience in the study of the collagen and elastic components of different soft tissues, including pterygium
We focus on the in-depth analysis of the two main fibrillar elements of the ECM, collagen fibers, as well as the main constituents of elastic fibers (TE, FBNs, and FBLNs), and the enzymes (LOXs) that carry out their assembly or crosslinking
This inflammatory microenvironment leads to the cooperative activation of other growth factors and other pathogenic mechanisms, such as angiogenesis, as well as the activation and functionality of stromal fibroblasts [78], which acquire a myofibroblast phenotype involved in the activation of various signaling pathways, such as mTOR [79], which modifies the composition of the ECM
Summary
Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva, which is related to chronic sun exposure, with frequent involvement of the corneal limbus that can invade the cornea. It usually shows a triangular wing shape, with the vertex opposite the base and directed toward the pupil and the base more frequently located in the nasal area toward the caruncle (Figure 1), it can arise from the temporal region. Pterygium can be unipolar if it affects only the nasal or temporal area of the conjunctiva or bipolar if it affects both It can develop in a single eye or appear bilaterally.
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