Establishment of in vitro model of corneal scar pathophysiology

Abstract

Corneal scarring is the major source of permanent blindness worldwide. The complex pathophysiology of corneal scarring is not comprehensibly understood as it involves the interaction of a constellation of pro-fibrotic cytokines influencing several signaling pathways involved in corneal scar development. In the present study, an attempt has been made to generate a relatively simple in vitro corneal scar model using primary corneal keratocytes by exogenously providing an optimized dose of combination of cytokines (TGF-β1, IL-6, and IL-8) involved in scar formation in situ. Data obtained from gene and protein expression analysis depicted enhanced ECM production with discrete expression of myofibroblast specific markers. The protein-protein interactions associated these proteins to various pathways involved in wound healing, cellular migration, and cytoskeletal remodeling justifying high relevance to in vivo scar formation. Hence the developed model can be used to acquire understanding about corneal scar pathophysiology and thus might be useful for designing the treatment modalities and efficacies for controlling scar formation.

Bioengineered in Vitro Tissue Models to Study SARS-CoV-2 Pathogenesis and Therapeutic Validation

“…In particular, the 3D bioprinted lung-like structures could be ideal in studying respiratory infections as they provide an air–tissue interface in complex, hollow architecture composed of multiple layers and cell types, which is far-fetched by traditional tissue engineering methods. In our laboratory, we have successfully fabricated various in vitro healthy 71 and diseased 72 tissue models using silk fibroin-gelatin bioink laden with specific cell types. These models closely recapitulated native tissues and ECM ultrastructure.…”

“… 19 Tissue engineering strategies can provide innovative solutions and can be well applied in this vicious situation involving a constellation of unknown questions. Tissue engineering can be employed for the development of a healthy tissue model (such as human hair follicle, 20 cartilage tissue 21 ) as well as a diseased tissue model (osteoarthritis model, 22 ophthalmic pathological condition 23 , 24 ), etc. Three-dimensional bioprinting enables even more advancements, as it entails the layer-by-layer specific positioning of the living cells, biochemistry, growth factors, orientation of ECM, etc.…”

Fibrosis: Shared Lessons From the Lens and Cornea

“…These models include manual circular keratectomy, incisional, and excimer laser induced models in rodents and rabbits (Wilson et al, ; Stepp et al, ; Ljubimov and Saghizadeh, ; Miyagi et al, ). Researchers have also developed ex vivo models using organ‐cultured corneas to study corneal fibrosis (Karamichos et al, ; Karamichos et al, ; Chawla and Ghosh, ). Chemical injuries have been used to look at fibrosis (Hamill et al, ; Gordon et al, ; Baradaran‐Rafii et al, ; Panahi et al, ).…”

“…Chemical injuries have been used to look at fibrosis (Hamill et al, ; Gordon et al, ; Baradaran‐Rafii et al, ; Panahi et al, ). Advances in cell and organ culture methodology are leading to models that are used to study both formation and resolution of fibrotic foci (Karamichos et al, ; Chawla and Ghosh, ) as shown in Figure A (Sriram et al, ).…”

Long‐term evaluation of corneal sub‐basal nerve recovery after photorefractive keratectomy and influence of pars plana vitrectomy

“…Clinical outcomes after photorefractive keratectomy (PRK) have been reported for up to 19 years and have confirmed, especially for myopia lower than 6.0 diopters (standard error of the mean [ SE ]), that the procedure is predictable, stable, and safe (Alió et al, ; Bricola, Scotto, Mete, Cerruti, & Traverso, ; Chawla & Ghosh, ; Chi & Trinkaus‐Randall, ; Guerin, Darcy, O'connor & O'Keeffe, ; Rajan, Jaycock, O'Brart, Nystrom, & Marshall, ; Vestergaard et al, ). However, compared with the long‐term clinical follow‐up data available, the structural corneal data obtained through in vivo confocal microscopy (IVCM) are, to our knowledge, limited to the first 5 years after PRK (Cruzat, Qazi, & Hamrah, ; Erie, McLaren, Hodge, & Bourne, ; Gambato et al, ; Guthoff, Zhivov, & Stachs, ; Linna & Tervo, ; Moilanen, Vesaluoma, Müller, & Tervo, ).…”