Biomechanical Modulation Therapy—A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns

Abstract

Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed.

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

“…Thus, aberrant stiffening of the limbus promotes excessive differentiation of LESCs, thereafter resulting in stem cell deficiency, corneal opacification, and vision loss ( Nowell et al, 2016 ). Collagenase treatment could rescue these alterations by softening the matrix, leading to inactivation of YAP signaling and inhibition of LESC differentiation ( Figure 1B ) ( Gouveia and Connon 2020 ). This research highlights the potential of regulating LESC function and corneal epithelial tissue regeneration by controlling tissue biomechanics and mechanotransduction.…”

Longitudinal assessment of the effect of alkali burns on corneal biomechanical properties using optical coherence elastography

“…The relative increase of Young's modulus 14 days postburn could be due to the development of chronic inflammation, neovascularization, and, most importantly, the increased fibrotic response associated with the wound healing process [16,56]. During the early repair phase (i.e., 8-20 days postburn) of the wound healing process, the normal structural elements of the stroma are replaced by excessive accumulation of the ECM matrix and distorted distribution of collagen fibers, resulting in fibrosis which is characterized by scarring and stiffening of tissue [2,16,56,60]. Different from the results of the current study, uniaxial tensile testing on porcine corneas demonstrated weakening of alkali-lesioned and cultured tissues compared with their healthy and fresh counterparts on day 7 post-AB [18].…”

“…In addition, exposure to alkali compounds causes the saponification of fatty acids in cell membranes and the destruction of the extracellular matrix (ECM) components. Depending on the dose and duration of exposure, such penetrating burns result in more significant epithelial disruption and destruction of the structure of the underlying stroma, which governs core corneal functions, including transparency, avascularity, shape, and mechanical strength [1][2][3][4]. These functions are attributed to the composition and structure of its ECM, which is mainly comprised of collagen fibrils that are regularly spaced apart by proteoglycans [5,6].…”

The Need for Improved Therapeutic Approaches to Protect the Cornea Against Chemotoxic Injuries

“…Deng et al 61 discuss an emerging therapeutic approach involving extracellular vesicles derived from mesenchymal stem cells, in particular, stromal stem cells, for corneal function and vision restoration. Gouveia and Connon 62 present an approach to biomechanical modulation therapy that promotes the regeneration of corneal/ocular tissues via restoration of the limbal stem cell niche. McDaniel et al 63 illustrate the potential of an ocular wound chamber for treating corneal surface injuries and infections, and Tripathi et al 64 highlight the importance of developing novel, multimodal, non-steroidal topical eye drops capable of utilizing concomitant mechanisms of action in preventing and treating corneal damages caused by toxic chemicals such as mustard gas in vivo.…”