Abstract
Purpose: To investigate the impact of tissue derived biological particles on enzyme-mediated weakened corneas. Methods: Rabbit corneas were treated with enzymes to create an ex vivo ectatic model that simulated representative characteristics of keratoconus (KC). Porcine cornea, cartilage, and lymph node tissues were processed to remove most cellular components and cryomilled into microparticles. The KC corneas were cultured in medium containing the tissue-derived biological particles (TDP) overnight. The mechanical, thermal, ultrastructural changes, and gene expressions of corneal stromal cells were characterized to evaluate the effects of the TDP treatment. Results: The enzyme treatment significantly reduced corneal mechanics and thermal stability, and also disrupted the extracellular matrix ultrastructure. After culturing with TDP medium, the Young’s modulus of the modeled KC corneas increased by ~50%, comparable to normal cornea controls. Similarly, the thermal denaturation temperature of the corneas was restored. These findings also corresponded to a significant increase in collagen fibril density after TDP treatment. Furthermore, corneas cultured in TDP medium significantly downregulated expression of the pro-inflammatory gene Tnfα, and restored the expression of the key keratocyte markers Aldh, keratocan, and biglycan. Conclusions: Tissue-derived biological particles reinforce mechanical and thermal properties of corneal tissue in an ex vivo model of KC. Through this study, we demonstrate and characterize the previously unexplored impact of tissue-derived biological scaffolds on corneal biomechanics, thermal stability, and gene expression, presenting a potential new therapy for ocular disease.
Highlights
The cornea is the outermost layer of the eye, which functions as a protective and light-refractive tissue
Collagen crosslinking initiated with riboflavin and ultraviolet-A (UVA) irradiation is a recently developed therapeutic method designed to slow or halt the progression of keratoconus or post laser-assisted in situ keratomileusis ectasia [5]
We investigate the potential of tissue-derived biological particles (TDPs) in restoring cornea physical and biological properties in an enzyme-mediated ex vivo corneal ectatic model
Summary
The cornea is the outermost layer of the eye, which functions as a protective and light-refractive tissue. Corneal stroma represents about 90% of the cornea thickness and is composed of a collagen-rich extracellular matrix (ECM) with highly aligned collagen fibrils forming densely packed lamellae [1] This unique stromal ultrastructure provides transparency and mechanical stability to the cornea. In the case of corneal development and corneal wound healing, proteoglycan ECM components secreted by keratocytes play an important role in regulating corneal fibril size and spacing. This ECM regulation has a critical impact on corneal optical and mechanical properties [9,10]. These results open the door to the potential therapeutic use of tissue-derived particles in cornea disease
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