Biomedical subjects

J Koretz

Publications and source records attributed to J Koretz.

4 recordsLinked to original sources

PubMed1993

Is primary open angle glaucoma caused by small proteins?

Primary open angle glaucoma is a disease which is characterized by a decreased facility of outflow of aqueous humor from the anterior segment of the eye. Analyses by gel exclusion chromatography of the aqueous humor of normal monkeys have shown that the proteins in this fluid range in size from approximately 40-200 kilodaltons. Although small proteins and peptides are seen in the aqueous humor by SDS gel electrophoresis, these smaller proteins appear to elute by column chromatography with the albumin peak. In the outflow of the aqueous humor, the trabecular meshwork may be an efficient sieve for proteins of intermediate size, but this tissue may be obstructed if the proteins present become too large or too small as a result of other disease processes in the eye. Primary open angle glaucoma may be the result of the inability of the trabecular meshwork to filter small proteins and polypeptides efficiently.

Animals↗

PubMed1988

Effects of phosphorylation of light chain residues threonine 18 and serine 19 on the properties and conformation of smooth muscle myosin.

Smooth muscle myosin can be phosphorylated by myosin light chain kinase at the serine 19 and threonine 18 residues of the two 20,000-dalton light chains (Ikebe, M., Hartshorne, D. J., and Elizinga, M. (1986) J. Biol. Chem. 261, 36-39). These studies with myosin and heavy meromyosin (HMM) compare the effects induced by phosphorylation of serine 19 (M2P and HMM2P) and serine 19 plus threonine 18 (M4P and HMM4P). Formation of M4P altered the KCl dependence of viscosity and Mg2+-ATPase and higher values were maintained at lower ionic strengths, compared to M2P or dephosphorylated myosin (Mo). This is consistent with the stabilization of the 6 S conformation. The tendency for aggregation, as judged by light scattering, followed the sequence M4P greater than M2P greater than Mo. Filaments formed with M4P were more resistant to dissociation by ATP compared to filaments of M2P. Phosphorylation of HMM2P doubled Vmax of actin-activated ATPase with little effect on the apparent affinity for actin. The Mg2+-ATPase of HMM4P exhibited a higher activity at low ionic strength compared to HMM2P and HMMo. Hydrodynamic differences were detected at low ionic strength in the presence of ATP by sedimentation velocity measurements with HMM4P, HMM2P, and HMMo. Proteolysis by papain indicated an increased susceptibility of the head-neck junction of HMM4P compared to HMM2P. These data suggest that the phosphorylation of threonine 18 in addition to serine 19 change the conformation of myosin and HMM and this is associated with altered biological properties.

Animals↗

PubMed1987

Presbyopia: an animal model and experimental approaches for the study of the mechanism of accommodation and ocular ageing.

During the last hundred years, observations on normal and a few aniridic human eyes, together with population studies on the age-dependent decline in accommodative amplitude, resulted in the formulation of theories of human accommodation, and led to the concept that presbyopia is an inevitable consequence of ageing. However, such studies failed to substantiate these theories and concepts or to reveal the fundamental mechanisms of accommodation and its age-dependent loss. Detailed understanding of these mechanisms and the environmental, dietary, and behavioural factors that may influence the development of presbyopia will require controlled studies and, in some cases, invasive experimental manipulations that can only be achieved through the use of an animal model. This paper reviews some of the evidence indicating that the rhesus monkey is a highly suitable primary animal model for such studies, as well as for studies on other aspects of ocular ageing, and reviews some of the techniques and experimental approaches that have already been adapted or developed for such studies.

Accommodation, Ocular↗

PubMedDate not supplied

The ageing lens.

The human lens grows by a process of epithelial cell division at its equator and the formation of generations of differentiated fibre cells. Despite the process of continuous remodelling necessary to achieve growth within a closed system, the lens can retain a high level of light transmission throughout the lifetime of the individual, with the ability to form sharp images on the retina. Continuous growth of the lens solves the problem imposed by terminal differentiation within a closed, avascular system, from which cells cannot be shed. The lens fibre tips arch over the equator to meet anteriorly and posteriorly and form branching sutures of increasing complexity. The stages of branching may create the optical zones of discontinuity seen on biomicroscopy. The lens is exposed to the cumulative effects of radiation, oxidation and postranslational modification. These later proteins and other lens molecules in such a way as to impair membrane functions and perturb protein (particularly crystallin) organisation, so that light transmission and image formation may be compromised. Damage is minimised by the presence of powerful scavenger and chaperone molecules. Progressive insolublisation of the crystallins of the lens nucleus in the first five decades of life, and the formation of higher molecular weight aggregates, may account for the decreased deformability of the lens nucleus which characterises presbyopia. Additional factors include: the progressive increase in lens mass with age, changes in the point of insertion of the lens zonules, and a shortening of the radius of curvature of the anterior surface of the lens. Also with age, there is a fall in light transmission by the lens, associated with increased light scatter, increased spectral absorption, particularly at the blue end of the spectrum, and increased lens fluorescence. A major factor responsible for the increased yellowing of the lens is the accumulation of a novel fluorogen, glutathione-3-hydroxy kynurenine glycoside, which makes a major contribution to the increasing fluorescence of the lens nucleus which occurs with age. Since this compound may also cross-link with the lens crystallins, it may contribute to the formation of high-molecular-weight aggregates and the increases in light scattering which occur with age. Focal changes of microscopic size are observed in apparently transparent, aged lenses and may be regarded as precursors of cortical cataract formation.

Aging↗