Exogenous collagen crosslinking reduces scleral permeability: modeling the effects of age-related crosslink accumulation

¹ Ophthalmology, University of California, San Francisco, 10 Koret Way, K301, San Francisco, California, 94143-0730, United States
² Mechanical Engineering, University of California, Berkeley, Berkeley, California, United States; Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, United States
³ Ophthalmology, University of California, San Francisco, San Francisco, California, United States

^* To whom correspondence should be addressed. E-mail: stewartj{at}vision.ucsf.edu.

	Abstract

Purpose: To investigate the relationship between scleral permeability and non-enzymatic crosslink density. Methods: Scleral discs 18 mm in diameter were dissected from the medial and lateral equatorial region of 60 cadaveric porcine eyes. Samples were incubated for 24 hours with control solution or methyglyoxal at concentrations of 0.001%, 0.01%, 0.10%, or 1.00%. Non-enzymatic crosslink density in treated and control groups was quantified via papain digest and fluorescence spectrophotometry. Treated scleral discs were mounted in a customized Ussing-type chamber connected to vertical tubing, and specific hydraulic conductivity was determined according to the descent of a column of degassed saline at room temperature. Permeability to diffusion of fluorescein in a static chamber was determined for another set of treated scleral samples. Results: Methylglyoxal treatment effectively increased non-enzymatic crosslink content as indicated by the average fluorescence for each group. Specific hydraulic conductivity (m2) was reduced with increasing crosslink density. Similarly, the permeability coefficient for the fluorescein solute consistently decreased with increasing methylglyoxal concentration, indicating diffusion impedance due to the treatment. Conclusions: Non-enzymatic crosslink density can be significantly increased by treating with methylglyoxal. Porcine sclera showed a nonlinear reduction in solute permeability and specific hydraulic conductivity with increasing crosslink density. This model suggests that age-related non-enzymatic crosslink accumulation can have a substantial impact on scleral permeability.

Key Words: drug delivery, sclera, crosslinks, permeability

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