Advanced Glycation End-Product Accumulation Reduces Vitreous Permeability

作者:Lee On Tat; Good Samuel D; Lamy Ricardo; Kudisch Max; Stewart Jay M*
来源:Investigative Ophthalmology & Visual Science, 2015, 56(5): 2892-2897.
DOI:10.1167/iovs.14-15840

摘要

PURPOSE. To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vitreous to small-and large-solute diffusion. METHODS. Vitreous from freshly excised porcine eyes was treated for 30 minutes with control or 0.01%, 0.1%, or 1% methylglyoxal (MG) solution. The efficacy of the glycation regimen was verified by measuring nonenzymatic cross-link density by fluorescence in the vitreous samples. Resistance to collagenase digestion as well as Ne-(carboxyethyl) lysine (CEL) content were also measured. The permeability coefficient for fluorescein and fluorescein isothiocyanate (FITC)-IgG diffusion through 3 mL of the vitreous samples was determined by using a custom permeability tester. RESULTS. Vitreous cross-linking with MG treatment was confirmed by increased fluorescence, increased CEL concentration, and increased resistance to collagenase digestion. Vitreous glycation resulted in a statistically significant decrease in the permeability coefficient for fluorescein diffusion when either 0.1% or 1% MG solution was used (5.36 +/- 5.24 x 10(-5) cm s(-1), P = 0.04; and 4.03 +/- 2.1 x 10(-1) cm s(-1), P = 0.001; respectively, compared with control, 9.77 +/- 5.45 x 10(-5) cm s(-1)). The permeability coefficient for diffusion of FITC-IgG between control (9.9 +/- 6.37 x 10(-5) cm s(-1)) and treatment groups was statistically significant at all MG concentrations (0.01% MG: 3.95 +/- 3.44 x 10(-5) cm s(-1), P = 0.003; 0.1% MG: 4.27 +/- 1.32 x 10(-5) cm s(-1), P = 0.004; and 0.1% MG: 3.72 +/- 2.49 x 10(-5) cm s(-1), P = 0.001). CONCLUSIONS. Advanced glycation end-product (AGE) accumulation reduces vitreous permeability when glycation is performed in ex vivo porcine vitreous. The permeability change was more pronounced for the larger solute, suggesting a lower threshold for AGE-induced permeability changes to impact the movement of proteins through the vitreous when compared with smaller molecules.

  • 出版日期2015-5