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 intraocular pressure due to a decreased facility of outflow of aqueous humor through the trabecular meshwork. The etiology of primary open-angle glaucoma is currently unknown, but it has been suggested that one possible mechanism may be the obstruction of flow through the trabecular meshwork by small macromolecules, analogous to the effect of 'fines' in column chromatography. One such candidate is alpha-crystallin, a lens 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 that alpha-crystallin and serum albumin, which is secreted at the anterior root of the iris and is believed to act as a protein escort through the trabecular meshwork in mammalian eyes, will interact at concentrations 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 interaction at or above this concentration. This binding could serve the necessary function of preventing interactions between alpha-crystallin monomers or small aggregates and hydrophobic surfaces within the trabecular meshwork. Since, however, the interaction between the two proteins is not extremely strong, the accumulation of unbound alpha-crystallin monomers and/or dimers could contribute to the development of primary open-angle glaucoma.
Doss
E W
EW
Department of Biology, Rensselaer Polytechnic Institute, Troy, N.Y. 12180-3590, USA. dosse@rpi.edu
Ward
K A
KA
Koretz
J F
JF
D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D002853:Chromatography, Liquid; D003459:Crystallins / Q000302:isolation & purification / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005902:Glaucoma, Open-Angle / Q000209:etiology* / Q000378:metabolism*; D007908:Lens, Crystalline / Q000737:chemistry; D046911:Macromolecular Substances; D010684:Philosophy; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
D003459:Crystallins; D046911:Macromolecular Substances; D012709:Serum Albumin