Decorin Protein Crosslinking for Corneal Rigidity
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Solution Overview
Problem
Current methods for stabilizing collagen fibrils in the cornea, such as those used in refractive surgery, often result in complications like regression, haze, and reduced corneal rigidity, which can lead to conditions like keratectasia and keratoconus, due to the disruption of collagen crosslinks and proteoglycan composition.
Innovation Solution
Administering decorin, a protein that crosslinks collagen fibrils by binding to two different fibrils to form a bridge between them, thereby increasing the rigidity of the cornea, which can be done before, during, or after refractive surgical procedures, or as a treatment for existing conditions like keratectasia and keratoconus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If refractive surgical procedures (PRK, LASIK) are performed to correct vision, then refractive error is corrected, but corneal rigidity is reduced and regression occurs
Solution Approach 1:
The patent applies crosslinking agents (riboflavin/UVA or transglutaminase) before or during refractive surgery to pre-strengthen the corneal collagen structure. This preliminary reinforcement prevents the loss of corneal rigidity that normally occurs after ablation procedures, allowing accurate refractive correction without subsequent regression or keratectasia
Solution Approach 2:
The patent creates a composite corneal structure by introducing exogenous crosslinking agents that form additional bonds between collagen fibrils. This composite approach combines the natural collagen matrix with artificial crosslinks, resulting in a cornea that maintains both optical clarity and enhanced mechanical strength after refractive surgery
2Manufacturing precision
If higher degrees of refractive correction are attempted, then more severe myopia is treated, but regression and corneal haze increase
Solution Approach 1:
By applying crosslinking agents before high-magnitude ablation, the corneal structure is pre-reinforced to withstand the stress of removing larger amounts of tissue. This prevents the collagen fibrils from becoming disorganized and forming haze, while also preventing regression even after aggressive correction of severe myopia
Solution Approach 2:
The crosslinking agents create a protective network within the corneal stroma that cushions against the mechanical stress and structural disruption caused by high-energy ablation. This protective framework prevents harmful effects like haze formation and regression that would otherwise occur with aggressive refractive correction
3Productivity
If corneal crosslinks are interrupted or proteoglycan composition is altered, then surgical procedure is completed, but keratectasia develops
Solution Approach 1:
The patent introduces crosslinking agents as intermediary substances that mediate between the surgical trauma and the corneal structural integrity. These agents form bridging connections between collagen fibrils, maintaining structural stability even when normal crosslinks are interrupted during surgery or when proteoglycan composition is altered by the surgical procedure
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of decorin effectively stabilizes collagen fibrils, reducing the risk of regression and haze, and enhancing corneal rigidity, thereby improving surgical outcomes and treating conditions associated with reduced corneal strength.
Implementation Method 1
The decorin crosslinks collagen fibrils by binding to each of two different fibrils to form a bridge there between
Data Source
AI summary
Methods of stabilizing collagen fibrils in a cornea comprising administering a composition comprising a protein that crosslinks collagen fibrils and a pharmaceutically acceptable carrier are disclosed. Patients that would benefit from the practice of the methods include patients' having a refractive surgical procedure, patients with keratectasia, and patients with keratodconus. In some embodiments, a protein that crosslinks collagen fibrils by binding to each of two different fibrils to form a bridge there between is use in the method. An example of a protein of this type is decorin. In other embodiments, a protein that crosslinks collagen fibrils by catalyzing the formation of a covalent bond between an amino acid in one collagen fibril and an amino acid in a second collagen fibril is used. Proteins that catalyze formation of covalent bonds between collagen fibrils include transglutaminase.