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Mariana Garcia, Amit Jha, Kevin Healy, Christine Wildsoet; Myopia control in guinea pigs with a biomimetic hyaluronic acid-based hydrogel. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4702.
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Increased eye elongation in myopia reflects increased scleral remodeling and thinning, as well as increased scleral creep in the largest, most mechanically unstable eyes, which are at increased risk of sight-threatening complications such as retinoschisis. The aim of this study is to optimize an injectible, biomimetic polymer-based treatment to rehabilitate the myopic sclera, by providing a synthetic matrix into which scleral cells can migrate and deposit new extracellular matrix.
HyA hydrogels with constant modulus but varying RGD concentrations were synthesized from acrylated hyaluronic acid (AcHyA) and acrylated hyaluronic acid conjugated to bsp-RGD(15) peptide (AcHyA-RGD) in varying ratios, crosslinked with a cysteine-terminated enzymatically-degradable peptide crosslinker. The moduli of each formulation were measured with parallel plate oscillatory rheology. Their biocompatibility was examined in vitro using primary cultures of guinea pig scleral fibroblasts seeded onto the polymerized hydrogels and cultured for 14 days. Cell proliferation rates were derived from an Alamar Blue (AbDserotec) assay performed at timed intervals. For in vivo testing, 7-day old guinea pigs were form deprived with diffusers for 4 weeks, before implantation surgery involving sub-Tenon’s capsule injection of 100 ul HyA hydrogel at the posterior pole of the eye. Ocular length was monitored for up to 2 weeks, when animals were euthanized and the eyes processed for histology, with Alcian Blue and Sirius Red as stains.
The modulus of the polymerized hydrogel was ~800Pa. After 14 days of culture, cells showed the highest proliferation rate on gels with the highest concentration of RGD (250uM), for which there was a 400% increase in cell number. In vivo, the implanted HyA hydrogel slowed ocular elongation and in one case, reduced ocular length. Follow-up histology verified the hydrogel to be still present 2 weeks post-surgery, as well as significant cell migration and collagen deposition in the implant.
The above data provide proof of principle for the possibility of synthesizing injectible HyA hydrogels that are biocompatible with scleral fibroblasts. Preliminary in vivo data suggest that they can stabilize the sclera.
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