Effect of high glucose concentration on corneal collagen biosynthesis

The effect of high glucose concentration (3 g/l) on bovine corneal total protein and collagen biosynthesis was studied, using 3H-proline incorporation in explant cultures with protein and collagen determinations. The high glucose concentration increased the incorporation of 3H-proline in total corneal proteins as well as in collagens. The specific radioactivity of stromal collagens was strongly increased in these conditions. Mannitol was used to control the osmotic effect of the high glucose concentration, both at 1 and 3 g/l concentrations. Mannitol did not increase the incorporation of 3H-proline in total proteins or collagens, but on the contrary decreased it. The high glucose concentration decreased the excretion of neosynthesized proteins and collagens in the culture medium, but did not affect the total protein or collagen content of the corneas. The strong increase in the specific radioactivity of corneal collagens in the presence of 3 g/l glucose suggests an increased turnover of collagens in diabetic corneas. The increased biosynthesis of collagens together with their decreased elimination in the extracellular compartment can create the conditions for the formation and accumulation of advanced glycation endproducts by the Maillard reaction. This can induce and stimulate the liquefaction of the vitreous body leading to sight-threatening disorders such as diabetic retinopathy, retinal detachment, glaucoma, cataract formation and age-related macular degeneration.