Interactions between Biomaterials and the Sclera: Implications on Myopia Progression
Myopia prevalence has steadily climbed worldwide in recent decades with the most dramatic impact in East Asian countries. Treatments such as eyeglasses, contact lenses, and laser surgery for the refractive error are widely available, but none cures the underlying cause. In progressive high myopia, invasive surgical procedures using a scleral buckle for mechanical support are performed since the patient is at risk of becoming blind. The treatment outcome is highly dependent on the surgeon's skills and the patient's myopia progression rate, with limited choices in buckling materials. This dissertation, in four main studies, represents efforts made to control high myopia progression through the exploration and development of biomaterials that influence scleral growth.
First, mRNA expression levels of the chick scleral matrix metalloproteinases, tissue-inhibitor of matrix metalloproteinases, and transforming growth factor-beta 2 were assessed for temporal and defocus power effects. The first study elucidated the roles that these factors play in scleral growth regulation and suggested potential motifs that can be incorporated in future biomaterials design. Second, poly(vinyl-pyrrolidone) as injectable gels and poly(2-hydroxyethyl methacrylate) as solid strips were implanted in chicks to demonstrate the concept of posterior pole scleral reinforcements. This second study found that placing appropriate biomaterials at the posterior pole of the eye could directly influence scleral remodeling by interacting with the host cells. Both studies advanced the idea that scleral tissue remodeling could be potentially controlled by well-designed biomaterials.
These findings led to the exploration of biomimetic hydrogels comprising enzymatically-degradable semi-interpenetrating polymer networks (edsIPNs) to determine their biocompatibility and effects on the chick posterior eye wall. This third study demonstrated the feasibility of stimulating scleral growth by applying biomimetic injectable materials. Fourth, the muscarinic antagonist drug, atropine, was encapsulated within the edsIPNs and delivered to the chick eye posterior pole to evaluate the local effect of atropine release. This fourth study offered an alternative method of ocular drug delivery for treatment of myopia, with the potential to elucidate the actual location of the inhibitive effect of atropine on myopia progression. In summary, this dissertation contributes to the design and use of biomaterials specific to myopia therapy and adds novel insights to scleral tissue engineering.