Investigation of the ‘Fines’ Hypothesis of Primary Open-Angle Glaucoma: The Possible Role of Alpha-Crystallin

Abstract

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 α-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 α-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 α-crystallin up to the critical micelle concentration for α-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 α-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 α-crystallin monomers and/or dimers could contribute to the development of primary open-angle glaucoma.

Polymorphic Glutathione S-transferase M1 is a Risk Factor of Primary Open-angle Glaucoma among Estonians

“…Primary open-angle glaucoma is a disease mainly caused by an increase in intraocular pressure due to a decreased facility of out¯ow of aqueous humour through the trabecular meshwork. The etiology of POAG is currently unknown, but it has been suggested that one possible mechanism may be the obstruction of¯ow through the trabecular meshwork by macromolecules (Doss, Ward and Koretz, 1998). Studies have identi®ed several forms of glutathione S-transferases belonging to the three major enzyme classes (Alpha, Mu and Pi) in iris, ciliary body and lens (Ahmad et al, 1989;Huang et al, 1993).…”

A contemporary concept of the blood–aqueous barrier

“…Following up on the initial report of Johnson, et al (1993), other investigators began to explore whether smaller plasma-derived proteins (termed “fines”) might contribute to normal aqueous outflow resistance (Doss, Ward and Koretz, 1998; Russell, Koretz and Epstein, 1993). While this work provided general support for the possibility that certain proteins could influence outflow resistance, additional work on the role of proteins being added to the aqueous humor just prior to the outflow pathway is warranted.…”

A study of aqueous humour proteins in patients of primary open angle glaucoma

“…In this context, it must be emphasised that the cellular consequences of heat and ischemia are similar. Albumin, the major aqueous humor protein, acts as a escort through the trabecular meshwork in mammalian eyes, and interacts with alpha-crystallin up to the critical micelle concentration for alpha-crystallin (3.5-5 mg/ml or 0.18-0.25 mM) as reported by Doss et al [29]. There is little in-teraction at or above this concentration.…”