Professor of Biology

Education and Training

Jane Koretz received her B.A. with high honors from Swarthmore College, and her Ph.D. in biophysics from The University of Chicago for her work on skeletal muscle myosin ATPase with Edwin W. Taylor.  She was a Muscular Dystrophy Association post-doctoral fellow at the MRC Cell Biophysics Unit, King’s College, London, before joining the faculty at Rensselaer, and was the recipient of a Fulbright for her sabbatical work at the Nuffield Laboratory of Ophthalmology (University of Oxford). 

Contact

Office: Science Center Rm. 3C13

Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180

Research Interests

Modeling the human visual process.

The young human eye is capable of focusing from infinity to the tip of one’s nose, a multifactorial process termed accommodation that involves changing the shape and thickness of the eye’s lens.  As people grow older, their ability to focus on near objects gradually diminishes, eventually leading to the need for reading glasses (presbyopia).   Changes in the lens and surrounding tissues with age have been implicated in presbyopia.  At the same time, the lens grows less transparent, which may ultimately lead to cataracts.   As a result, understanding the aging of human vision involves understanding aging processes ranging in scale from the tissue level down to the molecular level.

Mammalian lenses contain unusual proteins, termed crystallins, that contribute to the ability of the lens to refract light for focus on the retina while maintaining lens transparency at extremely high concentrations over a lifetime.   The major lens protein is alpha-crystallin, which is assigned to the small heat shock protein family because of its highly conserved core structure.  It may contribute to maintenance of lens clarity and transparency by binding damaged or denaturing proteins before they can aggregate into light-scattering clusters, but is itself affected by age-dependent modifications.   Outside of the eye, one of the alpha-crystallin isoforms (alphaB-crystallin) appears to be involved in similar processes in most of the major tissues, including skeletal and cardiac muscle, and is associated with a number of protein misfolding diseases.   We are using a combined molecular biological/biophysical approach to characterize the relationship between structure and function in the alpha-crystallins, and in particular to determine what special features of these proteins make them uniquely suited for the eye lens.

In order for the lens to focus light onto the retina, it must not only be transparent, but must also exhibit an index of refraction significantly greater than the surrounding aqueous and vitreous humors.  This is the result of internal protein concentrations in excess of 300 mg/ml.   In order to increase the refractive contribution of the lens, these lens proteins are distributed so as to create a refractive index gradient that appears to be maintained over the years despite lens growth and other aging effects.    Determining the shape of this refractive index gradient is a second area of interest in our lab.   It is particularly challenging because it is extremely difficult to measure the refractive index gradient in intact lenses, and there is some evidence that the characteristics of sample donated lenses are very different from lenses in vivo.  We are using information about the human focusing process that we collected in collaboration with Paul L. Kaufman, MD, of the University of Wisconsin to analyze factors influencing image formation using ray-tracing models developed from plausible refractive index profiles.

The proteins of the lens not only affect its functional longevity, but also its viscoelastic properties.  The lens develops from an inverted epithelial layer and, as a result, material in the center of the lens has been laid down pre-natally.  Indeed, the lens fiber cells are arranged so that the lens grows like the trunk of a tree, with the youngest cells also the most superficial.  In order for the lens to change its refractive contribution, it must change its curvature and thickness, a biomechanical process that will be affected by protein concentration, cytoplasmic viscosity, and the degree of force applied.  The lens grows throughout life, increasing in size and mass, and it is highly likely that this also contributes to diminution in focusing range with age.  However, it is also believed by some that the lens, in whole or part, also becomes more sclerotic, resistant to the changes in shape and curvature necessary for focus with increasing age.  Others have suggested that there is a change in the capability of the ciliary muscle controlling lens shape to effectively act on the lens, or a change in the properties of other tissues associated with focusing.  We have developed an analytical model of the focusing process that allows us to address some of these issues, using data about changes in lens shape and other factors, and are working to make it increasingly reflective of what is known about accommodation and aging in the human eye. 

Selected Publications

Koretz, J. F., Cook, C. A., Kaufman, P. L. Aging of the human lens: changes in lens shape at zero-diopter accommodation. J Opt Soc Am A Opt Image Sci Vis 18:265-72. [2001].

Koretz, J. F. and Cook, C. A.  Aging of the optics of the human eye:  lens refraction models and principal plane locations.  Optom. and Vis. Sci. (special issue on the aging eye), 78:396-404 [2001].

Burgio, M. R., Bennett, P.M., and Koretz, J.F.  Heat-induced quaternary transitions in hetero- and homo-polymers of  alpha-crystallin.  Mol. Vis., 7:228-233 [2001].

Koretz, J.F., Cook, C. A. and Kaufman, P. L.  Aging of the human lens:  changes in lens shape at zero diopters accommodation. J Opt Soc Am A Opt Image Sci Vis. 19(1):144-51 [2002]

Salerno, J. C., Salerno, K. M., Eifert, C.J.and Koretz, J. F.   Structural diversity in the small heat shock protein superfamily:  Control of aggregation by the N-terminal region.  Prot. Eng., 16(11): 847-51 [2003].

Koretz JF, Strenk SA, Strenk LM, Semmlow JL.  Scheimpflug and high-resolution magnetic resonance imaging of the anterior segment: a comparative study.  J Opt Soc Am A Opt Image Sci Vis. Mar;21(3):346-54 [2004].

Regini JW, Grossmann JG, Burgio MR, Malik NS, Koretz JF, Hodson SA, Elliott GF.  Structural changes in alpha-crystallin and whole eye lens during heating, observed by low-angle X-ray diffraction.  J Mol Biol. Mar 5;336(5):1185-94 [2004].

Strenk SA, Strenk LM, Koretz JF. The mechanism of presbyopia.  Prog Retin Eye Res. May;24(3):379-93 [2005]..

Eifert C, Burgio MR, Bennett PM, Salerno JC, Koretz JF.  N-terminal control of small heat shock protein oligomerization: changes in aggregate size and chaperone-like function. Biochim Biophys Acta. May 15;1748(2):146-56 [2005].

Yang C, Salerno JC, Koretz JF.  NH2-terminal stabilization of small heat shock protein structure: a comparison of two NH2-terminal deletion mutants of alphaA-crystallin. Mol Vis. 11:641-7 [2005].

Li, Ying K., K. R. Schmitz,  J. C. Salerno, and J. F. Koretz. The role of the conserved C-terminal triad in alpha-crystallin aggregation and functionality.  Mol. Vis.,  13:1758-1768 [2007].