Unraveling the mechanobiology of cornea: From bench side to the clinic

Abstract

The cornea is a transparent, dome-shaped structure on the front part of the eye that serves as a major optic element and a protector from the external environment. Recent evidence shows aberrant alterations of the corneal mechano-environment in development and progression of various corneal diseases. It is, thus, critical to understand how corneal cells sense and respond to mechanical signals in physiological and pathological conditions. In this review, we summarize the corneal mechano-environment and discuss the impact of these mechanical cues on cellular functions from the bench side (in a laboratory research setting). From a clinical perspective, we comprehensively review the mechanical changes of corneal tissue in several cornea-related diseases, including keratoconus, myopia, and keratectasia, following refractive surgery. The findings from the bench side and clinic underscore the involvement of mechanical cues in corneal disorders, which may open a new avenue for development of novel therapeutic strategies by targeting corneal mechanics.

Colocalization of corneal resistance factor GWAS loci with GTEx e/sQTLs highlights plausible candidate causal genes for keratoconus postnatal corneal stroma weakening

“…Biglycan also interacts with type VI collagen ( Wiberg et al, 2002 ), strongly causally implicated in CRF determination by our present analysis and that of rare coding variants ( van Hout et al, 2020 ) and both implicated in regulating ECM stiffness and maximal load ( Leiphart et al, 2021 ). The anchoring of cells to the ECM via bridging interactions is thought to play a critical role in mechanosensing and signaling, processes that have not been previously highlighted in the context of CRF or keratoconus GWAS interpretations but recognized important players in cornea biology ( Yang et al, 2022 ), and potential drivers of keratoconus pathology ( Dou et al, 2022 ). Among its multiple roles, THBS4 has been shown to influence trafficking of sarcoglycans in myocytes ( Brody et al, 2018 ), but the function of the specific isoform modulated by causal splicing variant highlighted by our study remains to be determined.…”

Biomechanical homeostasis in ocular diseases: A mini-review

“…Rubbing action triggers several mechanical insults, including IOP spikes, altered shear stress, and high hydrostatic tissue pressure. For instance, vigorous rubbing can skyrocket the IOP to more than 10 times of a normal resting IOP, generating more dramatic pressure strain on the cornea ( 7 ). Mechano-transducers like YAP in stromal cells and β-catenin in epithelial cells are associated with the regulation of substrate stiffness and protease production in KC ( 42 , 43 ).…”

“…Starting with the anterior compartment, the cornea is the outermost component of the eye globe. Exposed to the open air, the cornea directly bears the exterior stimuli generated by atmospheric pressure ( 7 ), eye movement ( 8 ), and tear film motion ( 9 ), etc. To counterbalance, the internal stresses were fostered by aqueous humor ( 10 ) and IOP ( 7 ).…”

“…Exposed to the open air, the cornea directly bears the exterior stimuli generated by atmospheric pressure ( 7 ), eye movement ( 8 ), and tear film motion ( 9 ), etc. To counterbalance, the internal stresses were fostered by aqueous humor ( 10 ) and IOP ( 7 ). As the continuous tissue of the cornea, the anterior sclera also percepts comparable stresses and strains ( 11 ).…”

A Novel Technique of Amniotic Membrane Preparation Mimicking Limbal Epithelial Crypts Enhances the Number of Progenitor Cells upon Expansion

“…It is known that the physical cues of the cellular environment guide stem cell fate [33][34][35]. It is also suggested that biomechanical changes in the limbal stromal niche affect hLESCs fate [36]. No less importantly, mechanical and environmental changes in the corneal tissue have implications for some corneal diseases and pathologies [37].…”