Increased Hydrostatic Pressure Reduces Lens Hydration During Aging
The response to increased pressure in the human lens is non-linear and is age-dependent. The normal human lens of a 39-year-old imaged under 2 atmospheres (atm) pressure exhibited a pressure-dependent, linear reduction in spin-spin relaxation time T2 [338]. The reduction in spin-spin relaxation time T2 may imply a shift in water molecule hydration via intramolecular hydrogen bonding that restricts proton motions that result in stronger hydrogen bonding [339][340]. Although the increased pressure does not affect total water concentration in the lens, enhanced, stronger hydrogen bonding can increase the amount of bound water molecules. Consequently, increased pressure actually decreases the ratio of free to bound water, effectively reducing dehydration in the young lens. Unexpectedly, this phenomenon is reversed or even absent in the normal, older lens (77 years old), resulting in the release of bound water to increase free, unbound water that effectively enhances dehydration with increasing pressure [338]. Essentially, under increased pressure, a young lens responds by increasing the strength of hydrogen bonds to enhance hydration. Conversely, the aging lens is unable to compensate for hydrostatic pressure increases, resulting in increased free water that exacerbates dehydration in the lens where high molecular crowding and dehydration favor phase separation and aberrant crystallin protein aggregation. What is unclear is why an aging lens is incapable of responding to increased pressure as opposed to a younger lens.