Changes in Lens That Accompany Galactitol Accumulation and Osmotic Swelling
As cataract formation progresses due to galactitol synthesis and subsequent osmotic swelling, changes occur in the lens epithelial cells. For instance, when rabbit lenses are placed in high-galactose mediums, a nearly 40% reduction in lens amino acid levels is observed, along with significant ATP reduction as well. Researchers theorized that this reduction in amino acid and ATP levels during cataract formation is a result of osmotic swelling. To test this theory, Kinoshita placed rabbit lenses in a high-galactose environment, but inhibited the osmotic swelling by constantly regulating galactose and galactitol concentrations. The results show that amino acid levels remained relatively constant and in some cases even increased.
Thus, from these experiments it would appear that the loss of amino acids in the lens when exposed to galactose is primarily due to the osmotic swelling of the lens brought about by dulcitol retention.
Interestingly, galactosemic patients will also present with amino aciduria and galactitoluria (excessive levels of amino acids and galactitol in the urine).
Osmotic swelling of the lens is also responsible for a reduction in electrolyte concentration during the initial vacuolar stage of galactosemic cataract. The water that is osmotically flowing into the lens fibers is not accompanied by ions such as Na+, K+, and Cl-, and so the electrolyte concentration inside the lens is simply diluted by the influx of water. The net concentration of the individual ions does not change during the initial vacuolar stage however. In Fig. 7, note the decrease in electrolyte concentration due to osmotic swelling during the initial vacuolar stage of galactosemic cataract. But when comparing it to the dry weight of the ions, note that there is no change in individual ion concentration at this stage. However, Kinoshita’s experiments showed a remarkable upswing in electrolyte concentration toward the latter stages of the galactosemic cataract and in the nuclear stage in particular. This observation seems to be explained by the continuous increase in lens permeability due to the osmotic swelling from galactitol accumulation. Cation and anion distribution becomes erratic, with Na+ and Cl- concentrations increasing while K+ concentration decreases as seen in Figures 8 and 9. Researchers have postulated that as the cataractous lens loses its ability to maintain homeostasis, electrolyte concentration eventually increases within the lens, which further encourages osmotic movement of water into the lens fibers, increasing lens permeability even more so. This damaging cycle may play a pivotal role in accelerating the rupture of lens fibers during the most advanced, nuclear stage of the galactosemic cataract.
Read more about this topic: Galactosemic Cataract
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—Philip Dormer Stanhope, 4th Earl Chesterfield (16941773)
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—Henry David Thoreau (18171862)