Untitled Document

Research

Paul L. Kaufman

M.D., New York University
Professor, Departments of Ophthalmology and Visual Sciences and Animal Health and Biomedical Sciences
kaufmanp@mhub.ophth.wisc.edu
http://wieyemd.ophth.wisc.edu/faculty/kaufman

Aging of the Near-Vision Focusing Mechanism

Accommodation, the process by which the eye focuses on near objects, occurs in humans through the controlled alteration of the crystalline lens. There is an age-related decline in accommodation (presbyopia), but its etiology remains unclear. The classic theory for the development of presbyopia involves a progressive hardening of the lens with aging. However, recent and ongoing research points to another cause.

The rhesus monkey appears to be a good animal model for human accommodation, presbyopia, and senile cataractogenesis. As the eyes of younger monkeys change focus, the ciliary muscle contracts, allowing the lens to thicken. Even though essentially normal in structure and contractility, in older monkeys the ciliary muscle is nearly completely immobile, and the lens does not thicken.

The ciliary muscle attaches to the back of the eye via an elastic membrane. We suspect that this membrane may become inelastic with age, rendering ciliary muscle contraction ineffective in promoting lens thickening. Intact old ciliary muscle does not contract when exposed to pilocarpine. However, severing this posterior attachment in old eyes exposed to pilocarpine allows the muscle to contract. This finding may have enormous implications with regard to the pathophysiology and treatment of not only presbyopia but also primary open angle glaucoma.

Damage from excess pressure in the eyeball is a frequent cause of blindness, especially in older people. Anteriorly, ciliary muscle tendons connect with the trabecular meshwork (a sieve-like structure), and Schlemm's canal (a small vein), a drainage pathway for aqueous humor. If drainage is blocked, there can be irreversible damage to the optic nerve and blindness. We speculate that each time the ciliary muscle contracts it spreads the meshwork and widens the canal, thus flushing out the meshwork with a rush of fluid. The loss of ciliary muscle mobility with age may cause this drainage network to clog, resulting in increased pressure in the eye and glaucoma.

Related collaborative work includes cholinomimetic drug-induced accommodation as a bio-marker in a study of nutritional influences on the aging of rhesus monkeys. We are also testing a moldable polymeric replacement lens to determine if accommodation can be restored in old monkeys.

Representative Publications
Wendt, M., Croft, M.A., McDonald, J., Kaufman, P.L., & Glasser, A. (2008). Lens diameter and thickness as a function of age and pharmacologically stimulated accommodation in rhesus monkeys. Experimental Eye Research, 86(5), 746-752.

Kaufman, P.L. (2008). Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia: Interrogating Mother Nature: asking why, asking how, recognizing the signs, followi Experimental Eye Research, 86(1), 3-17.

Tian, B., Gabelt, B.T., Geiger, B., & Kaufman, P.L. (2008). The role of the actomyosin system in regulating trabecular fluid outflow. Experimental Eye Research, 2008 August 27 [Epub ahead of print].

Tian, B., & Kaufman, P.L. (2007). Combined effects of H7 and pilocarpine on anterior segment physiology in monkey eyes. Current Eye Research, 32(6), 491-500.

Nickells, R.B, Schlamp, C.L., Li, Y., Kaufman, P.L., Heatley, G., Peterson, J.C., Faha, B., & Ver Hoeve, J.N. (2007). Surgical lowering of elevated intraocular pressure in monkeys prevents progression of glaucomatous disease. Experimental Eye Research, 84(4), 729-736.

Gupta, N., Ly, T., Zhang, Q., Kaufman, P.L., Weinreb, R.N., & Yucel, Y.H. (2007). Chronic ocular hypertension induces dendrite pathology in the lateral geniculate nucleus of the brain. Experimental Eye Research, 84(1), 176-184.

Croft, M.A., Glasser, A., Heatley, G., McDonald, J., Ebbert, T., Dabl, D.B., Nadkarni, N.V., & Kaufman, P.L. (2006). Accommodative ciliary body and lens function in rhesus monkeys, I: Normal lens, zonule and cililary process configuration in the iridectomized eye. Investigative Ophthalmology & Visual Science, 47(3), 1076-1086.

Croft, M.A., Glasser, A., Heatley, G., McDonald, J., Ebbert, T., Nadkarni, N.V., & Kaufman, P.L. (2006). The zonula, lens, and normal iridectomized circumlental space in the rhesus monkey eye. Investigative Ophthalmology & Visual Science, 47(3), 1087-1095.

Sabanay, I., Tian, B., Gabelt, B.T., Geiger, B., & Kaufman, P.L. (2006). Latrunculin B effects on trabecular meshwork and corneal endothelial morphology in monkeys. Experimental Eye Research, 82(2), 236-246.

Tian, B., Hu, Y., Gabelt, B.T., & Kaufman, P.L. (2006). Factors affecting outflow facility calculations. Experimental Eye Research, 83(6), 1515-1520.

Filla, M.S., Kaufman, P.L., Woods, A., & Peters, D.M.P. (2006). b1 and b 3 integrins cooperate to induce a unique syndecan-4 containing cross-linked actin networks (CLANS) in human trabecular meshwork (HTM) cells. Invest. Ophthalmol. Vis. Sci., 47, 1956-1967.

Gabelt, B.T., Hu, Y., Vittitow, J.L., Rasmussen, C.A., Grosheva, I., Bershadsky, A.D., Geiger, B., Borr�s, T., & Kaufman, P.L. (2006). Caldesmon transgene expression disrupts focal adhesions in HTM cells and increases outflow facility in organ-cultured human and monkey anterior segments. Experimental Eye Research, 82(6), 935-944.

Grosheva, I., Vittitow, J.L., Goichberg, I., Borr�s, T., Kaufman, P.L., Geiger, B., & Bershadsky, A.D. (2006). Caldesmon effects on the actin cytoskeleton and cell adhesion in cultured HTM cells. Experimental Eye Research, 82(6), 945-958.

Agapova, O.A., Kaufman, P.L., & Hernandez, M.R. (2006). Androgen receptor and NFkB expression in human normal and glaucomatous optic nerve head astrocytes in vitro and in experimental glaucoma. Experimental Eye Research, 82(6), 1053-1059.

May, C.A., Gottanka, J., Kaufman, P.L., L�tjen-Drecoll, E., & Scholz, M. (2006). Choroidal innervation and optic neuropathy in macacque monkeys with laser- or anterior chamber perfusion-induced short-term elevation of intraocular pressure. Experimental Eye Research, 82(6), 1060-1067.

Hu, Y., Gabelt, B.T., & Kaufman, P.L. (2006). Monkey organ-cultured anterior segments: technique and response to H-7. Experimental Eye Research, 82(6), 1100-1108.

Gabelt, B.T, & Kaufman, P.L. (2005). Changes in aqueous humor dynamics with age and glaucoma. Prog. Re.t Eye Res., 24, 612-637.

Kiland, J.A., Gabelt, B.T., & Kaufman, P.L. (2005). Effect of age on outflow resistance washout during anterior chamber perfusion in rhesus and cynomolgus monkeys. Exp. Eye Res., 81, 724-730.

Mattison, J.A., Croft, M.A., Dahl, D.B., Roth, G.S., Lane, M.A., Ingram, D.K., & Kaufman, P.L. (2005). Accommodative function in rhesus monkeys: Effects of aging and calorie restriction. Age: J. Am. Aging Assoc., 27, 59-67.

Gabelt, B.T., Gottanka, J., Ltjen-Drecoll, E., & Kaufman, P.L. (2003). Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys. Invest. Ophthalmol. Vis. Sci., 44, 2118-2125.

Koretz, J.F., Cook, C.A., & Kaufman, P.L. (2002). Aging of the human lens: Changes in lens shape upon accommodation and with accommodative loss. J. Opt. Soc. Am. A, Opt. Image Sci. Vis., 19, 144-151.

Koretz, J.F., Cook, C.A., Kaufman, P.L. (2001). Aging of the human lens: Changes in lens shape at zero diopters accommodation. J. Optical Soc. Am.-A., 18, 265-272.

Glasser, A., Croft, M.A., Brumback, L., & Kaufman, P.L. (2001). Ultrasound biomicroscopy of the aging rhesus monkey ciliary region. Optom. Vision Sci., 78(6), 417-24.

Glasser, A. & Kaufman, P.L. (1999). The mechanism of accommodation in primates. Ophthalmology, 108, 863-872.

Croft, M.A., Kaufman, P.L., Crawford, K.S., Neider, M.W., Glasser, A., & Bito, L.Z. (1998). Accomodation dynamics in aging rhesus monkeys. Am. J. Physiol., 275(44), R1885-R1897.

Croft, M.A., Oyen, M.J., Gange, S.J., Fisher, M.R., & Kaufman, P.L. (1996). Aging effects on accommodation and outflow facility responses to pilocarpine in humans. Arch. Ophthalmol., 114, 586-592.

Tamm, E., Croft, M.A., JungKunz, W., L�tjen-Drecoll, E., & Kaufman, P.L. (1992). Age-related loss of ciliary muscle mobility in the rhesus monkey. Role of the choroid. Arch. Ophthalmol., 110, 871-876.

Neider, M.W., Crawford, K., Kaufman, P.L., & Bito, L.Z. (1990). In vivo videography of the rhesus monkey accommodative apparatus. Age-related loss of ciliary muscle response to central stimulation. Arch. Ophthalmol., 108, 69-74.

L�tjen-Drecoll, E., Tamm, E., & Kaufman, P.L. (1988). Age changes in rhesus monkey ciliary muscle: light and electron microscopy. Exp. Eye Res., 47, 885- 899.

L�tjen-Drecoll, E., Tamm, E., & Kaufman, P.L. (1988). Age-related loss of morphologic responses to pilocarpine in rhesus monkey ciliary muscle. Arch. Ophthalmol., 106, 1591-1598.

Koretz, J.F., Bertasso, A.M., Neider, M.W., True-Gabelt, B., & Kaufman, P.L. (1987). Slit-lamp studies of the rhesus monkey eye. II. Changes in crystalline lens shape, thickness and position during accommodation and aging. Exp. Eye Res., 45, 317-326.

Bito, L.Z., DeRousseau, C.J., Kaufman, P.L., & Bito, J.W. (1982). Age dependent loss of accommodative amplitude in rhesus monkeys: an animal model for presbyopia. Invest. Ophthalmol. Vis. Sci., 23, 23-31.

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