INVESTIGATION OF THE FINES HYPOTHESIS OF PRIMARY OPEN-ANGLE GLAUCOMA - THE POSSIBLE ROLE OF ALPHA-CRYSTALLIN

Primary open-angle glaucoma is a disease caused by an increase in intr aocular pressure due to a decreased facility of outflow of aqueous hum or through the trabecular meshwork, The etiology of primary open-angle glaucoma is currently unknown, but it has been suggested that one pos sible mechanism may be the obstruction of flow through the trabecular meshwork by small macromolecules, analogous to the effect of 'fines' i n column chromatography, One such candidate is alpha-crystallin, a len s protein which may be released into the aqueous humor from lens fiber cells at concentrations below that necessary for the formation of the native aggregate, Results of in vitro binding experiments indicate th at alpha-crystallin and serum albumin, which is secreted at the anteri or root of the iris and is believed to act as a protein escort through the trabecular meshwork in mammalian eyes, will interact at concentra tions of alpha-crystallin up to the critical micelle concentration for alpha-crystallin (3.5-5 mg/ml, or 0.18-0.25 mM), There is little inte raction at or above this concentration. This binding could serve the n ecessary function of preventing interactions between alpha-crystallin monomers or small aggregates and hydrophobic surfaces within the trabe cular meshwork, Since, however, the interaction between the two protei ns is not extremely strong, the accumulation of unbound alpha-crystall in monomers and/or dimers could contribute to the development of prima ry open-angle glaucoma.