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Randy Christopher Bowen, Won Yong Lee, David W Grainger, Barbara M Wirostko; Assessing ocular hyaluronidase to develop a hyaluronan-based polymer drug delivery platform. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1295.
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Current treatments for ophthalmologic diseases require frequent and long-term therapy causing inconvenience and financial burden to patients. Cross-linked hyaluronan (CMHA) matrix such as Hystem® enables us to design sustained release drug delivery system potentially enhancing the efficacy of the treatment. Drug release from CMHA matrix largely depends upon the degradation of CMHA matrix by hyaluronidases (HAase) present in various ocular tissues. However, the presence of ocular HAase is poorly understood. Our study aims to address this issue by investigating the concentrations of HAase (Hyal-1) in various ocular tissues.
Human aqueous humor (hAH), vitreous (hV), sclera (hS), and cornea (hC), and monkey (RxGen, St. Kitts) aqueous humor (mAH), vitreous (mV), sclera (mS), cornea (mC), and lens (mL) were collected from cadaver eyes and prepared to prevent cross-contamination. HAase concentrations in all human ocular samples (hAH=5, hV=8, hS=2, hC=2) and 24 monkey ocular samples (mAH=7, mV=7, mS=3, mC=4, mL=3) were determined using commercially available ELISA kits (R&D, MN, USA; Cusabio, China).
Hyal-1 was present in all parts of the ocular tissues tested except in the lens. The concentration of Hyal-1 was homogeneous in human samples but varied in monkey tissue samples. In human tissues, Hyal-1 concentrations were 1.4-2.3 ng/mL in hAH; 3.2-4.7 ng/mL in hV; 1.9-2.3 ng/mL; 1.2-4.4 ng/mL in hC. In monkey tissues, Hyal-1 were 1.8-15.2 ng/mL in mAH; 4.6-5.0 ng/mL in mV; 2.7-4.3 ng/mL in mS; 9.9-12.2 ng/mL in; but undetectable in mL.
Ocular Hyal-1 concentration varies depending on the tissues in the eye. We provide quantitative data on HAase levels that correlate to enzymatic activity within the eye. These data will support our effort to optimize drug delivery system using CMHA matrix for diseases occurring in various ocular tissues thereby reducing treatment frequency and enhancing therapeutic efficacy.
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