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Training Grant-
Biology of Aging

Paul Kaufman

Paul L. Kaufman

M.D., New York University
Professor Emeritus, Departments of Ophthalmology & Visual Sciences and Animal Health & Biomedical Sciences

The Ageing Eye - Glaucoma and the Near-Vision Focusing Mechanism

Our laboratory studies the physiology, pharmacology, cell biology, neural control and aging of the primate aqueous humor formation and drainage system that is involved in glaucoma (an age-related disease in which fluid builds up in eye causing an increase in eye pressure and subsequent degeneration of the optic nerve), and the accommodative apparatus involved in presbyopia (the age-related inability to focus on near objects), seeking to gain new pathophysiological insights and to develop novel pharmacologic therapies for both human glaucoma and presbyopia.

Glaucoma is a characteristic degeneration of the optic nerve, which transmits visual impulses from the eye to the brain. Elevated eye pressure, from fluid buildup in the eye, is the most important causal risk factor, damaging the nerve in a variety of ways leading to eventual blindness. This disease can go undiagnosed, as it is asymptomatic in the early stages. Many people may have the disease and not know it until permanent damage has occurred.

The flow of fluid out of the eye decreases with age and in glaucoma. Variations or excesses in normal aging processes may shift the balance toward the initiation of glaucoma and its progression. These processes can result in accumulation of extracellular material in the outflow pathways, which contributes to the reduction in outflow and the resultant increase in intraocular pressure. 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. Our laboratory is actively involved in developing novel therapeutic strategies for glaucoma in both the pharmacologic and drug delivery arenas (e.g. gene therapy).

Presbyopia, the age-related loss of accommodation, or the ability to focus on near objects, is the most common ocular affliction in the world, affecting every individual over the age of 45-50 years, and its pathophysiology may be linked to that of glaucoma. Accommodation, the process by which the eye focuses on near objects, occurs in humans through the controlled alteration of the crystalline lens. 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. As the eye changes focus, the ciliary muscle contracts, allowing the lens to 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.

Representative Publications
Weinreb, R. N., Liebmann, J. M., Martin, K. R., Kaufman, P. L., & Vittitow, J. L. (2018). Latanoprostene bunod 0.024% in subjects with open-angle glaucoma or ocular hypertension: Pooled phase 3 study findings. Journal of Glaucoma, 27(1), 7-15.
View publication via DOI: DOI:10.1097/ijg.0000000000000831

Keller, K. E., Bhattacharya, S. K., Borras, T., Brunner, T. M., Chansangpetch, S., Clark, A. F., ... Kaufman, P. L. ... Stamer, W. D. (2018). Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Experimental Eye Research. Advance online publication.
View publication via DOI: DOI:10.1016/j.exer.2018.03.001

Aktas, Z., Rao, H., Slauson, S. R., Gabelt, B. T., Larsen, I. V., Sheridan, R. T. C., ... Kaufman, P. L. ... Brandt, C. R. (2018). Proteasome inhibition increases the efficiency of lentiviral vector-mediated transduction of trabecular meshwork. Investigative Ophthalmology & Visual Science, 59(1), 298-310.
View publication via DOI: DOI:10.1167/iovs.17-22074

Siegfried, C. J., Shui, Y. B., Tian, B., Nork, T. M., Heatley, G. A., & Kaufman, P. L. (2017). Effects of vitrectomy and lensectomy on older rhesus macaques: Oxygen distribution, antioxidant status, and aqueous humor dynamics. Investigative Ophthalmology & Visual Science, 58(10), 4003-4014.
View publication via DOI: DOI:10.1167/iovs.17-21890

Kaufman, P. L. (2017). Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension. Expert Opinion on Pharmacotherapy, 18(4), 433-444.
View publication via DOI: DOI:10.1080/14656566.2017.1293654

Croft, M. A., Lutjen-Drecoll, E., & Kaufman, P. L. (2017). Age-related posterior ciliary muscle restriction - A link between trabecular meshwork and optic nerve head pathophysiology. Experimental Eye Research, 158, 187-189.
View publication via DOI: DOI:10.1016/j.exer.2016.07.007

Croft, M. A., Heatley, G., McDonald, J. P., Katz, A., & Kaufman, P. L. (2016). Accommodative movements of the lens/capsule and the strand that extends between the posterior vitreous zonule insertion zone & the lens equator, in relation to the vitreous face and aging. Ophthalmic and Physiological Optics, 36(1), 21-32.
View publication via DOI: DOI:10.1111/opo.12256

Flugel-Koch, C., Croft, M.A., Kaufman, P.L., & Lutjen-Drecoll, E. (2016). Anteriorly located zonular fibers as a tool for fine regulation of accommodation. Ophthalmic and Physiologic Optics, 36(1), 13-20.
View publication via DOI: DOI:10.1111/opo.12257

Croft, M.A., Heatley, G.A., McDonald, J.P., Katz, A., & Kaufman, P.L. (2016). Accommodative movement of the lens/capsule and the PVZ INS-LE in relation to the vitreous face and aging. Ophthalmic and Physiologic Optics, 36(1), 21-32.
View publication via DOI: DOI:10.1111/opo.12256

McDonald, J.P., Kiland, J.A., Kaufman, P.L., Bentley, E., Elinwood, N., & McLellan, G. (2016). Effect of topical latanoprost 0.005% on intraocular pressure and pupil diameter in normal and glaucomatous cats. Veterinary Ophthalmology, 19(S1), 13-23.
View publication via DOI: DOI:10.1111/vop.12292

Weinreb, R.N., Ong, T., Scassellati Sforzolini, B., Vittitow, J.L., Singh, K., Kaufman, P.L., & Voyager Study Group (2015). A randomized, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. British Journal of Ophthalmology, 99(6), 9738-745.
View publication via DOI: DOI:10.1136/bjophthalmol-2014-305908

Lu, W., Hu, H.L., Sevigny, J., Gabelt, B.T., Kaufman, P.L., Johnson, E.C., Morrison, J.C., Zode, G.S., Sheffield, V.C., Zhang, X., Laties, A.M., & Mitchell, C.H. (2015). Rat, mouse and primate models of chronic glaucoma all show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye. Investigative Ophthalmology and Visual Science, 56(5), 3075-3083.
View publication via DOI: DOI:10.1167/iovs.14-15891

Slauson, S.R., Peters, D.M., Schwinn, M., Kaufman, P.L., Gabelt, B.T., & Brandt, C.R. (2015). Viral vector effects on exoenzyme C3 transferase-mediated actin disruption and on outflow facility. Investigative Ophthalmology and Visual Science, 56(5), 2431-2438.
View publication via DOI: DOI:10.1167/iovs.14-15909

Wang, Y., Yang, Q., Wang, Ying., Guo, L., Yin, Y., Fan, N., Zhou, X., Cai, S.P., Kaufman, P.L., & Liu, X. (2014). Neuroprotective effects of C3 exoenzyme in excitotoxic retinopathy. Experimental Eye Research, 125, 128-134.
View publication via DOI: DOI:10.1016/j.exer.2014.05.018

Rasmussen, C.A., Kaufman, P.L., Ritch, R., Haque, R., Brazzell, R.K., & Vittitow, J.L. (2014). Latrunculin B reduces intraocular pressure in human ocular hypertension and primary open angle glaucoma. Translational Vision Science Technology, 3(5), 1-9.
View publication via DOI: DOI:10.1167/tvst.3.5.1

Braunger, B.M., Ademoglu, B., Fuchshofer, R., Gabelt, B.T., Kiland, J.A., Hennes-Beean, E.A., Brunner, K.G., Kaufman, P.L., & Tamm, E.R. (2014). Identification of adult stem cells in Schwalbe's line region of the primate eye. Invest Ophthalmology Visual Science, 55(11), 7499-7507.
View publication via DOI: DOI:10.1167/iovs.14-14872

Croft, M. A., Nork, T. M., McDonald, J. P., Katz, A., Lutjen-Drecoll, E., & Kaufman, P. L. (2013). Accommodative movements of the vitreous membrane, choroid, and sclera in young and presbyopic human and nonhuman primate eyes. Investigative Ophthalmology and Visual Science, 54(7), 5049-5058.
View publication via DOI: DOI:10.1167/iovs.12-10847

Croft, M. A., McDonald, J. P., Katz, A., Lin, T. L., Lutjen-Drecoll, E., & Kaufman, P. L. (2013). Extralenticular and lenticular aspects of accommodation and presbyopia in human versus monkey eyes. Investigative Ophthalmology and Visual Science, 54(7), 5035-5048.
View publication via DOI: DOI:10.1167/iovs.12-10846

Tian, B., & Kaufman, P.L. (2012). Comparisons of actin filament disruptors and Rho kinase inhibitors as potential antiglaucoma medications. Expert Review of Ophthalmology, 7(2), 177-187.
View publication via DOI: DOI:10.1586/eop.12.12

Kaufman, P.L., & Rasmussen, C.A. (2012). Advances in glaucoma treatment and management: outflow drugs. Investigative Ophthalmology & Visual Science, 53(5), 2495-2500.
View publication via DOI: DOI:10.1167/iovs.12-9483m

Read, S.A., Williams, D.R., Wojtkowski, M., Roorda, A., Nichols, J.J., Mutti, D.O., Kaufman, P.L., & Carney, L.G. (2012). Imaging and measurement in the eye: now and ahead. Optometry & Vision Science, 89(5), 521-3.
View publication via DOI: DOI:10.1097/OPX.0b013e318257bab6

Sureshkumar, J., Haripriya, A., Muthukkaruppan, V., Kaufman, P.L., & Tian, B. (2012). Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro. Graefe's Archive for Clinical and Experimental Ophthalmology, 250(4), 507-514.
View publication via DOI: DOI:10.1007/s00417-011-1869-4

Weinreb, R.N., & Kaufman, P.L. (2011). Glaucoma research community and FDA look to the future, II: NEI/FDA Glaucoma Clinical Trial Design and Endpoints Symposium: measures of structural change and visual function. Investigative Ophthalmology & Visual Science, 52(11), 7842-7851.
View publication via DOI: DOI:10.1167/iovs.11-7895

Kiland, J.A., Gabelt, B.T., & Kaufman, P.L. (2011). Relationship of aqueous outflow resistance to age and total volume perfused in rhesus and cynomolgus monkeys. Investigative Ophthalmology & Visual Science, 52(9), 6820-6824.
View publication via DOI: DOI:10.1167/iovs.11-7811

Ly, T., Gupta, N., Weinreb, R.N., Kaufman, P.L., & Yucel, Y.H. (2011). Dendrite plasticity in the lateral geniculate nucleus in primate glaucoma. Vision Research, 51(2), 243-250.
View publication via DOI: DOI:10.1016/j.visres.2010.08.003

Lutjen-Drecoll, E., Kaufman, P.L., Wasielewski, R., L., T.L., & Croft, M.A. (2010). Morphology and accommodative function of the vitreous zonule in human and monkey eyes. Investigative Ophthalmology & Visual Science, 51, 1554-1564.
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View publication via DOI: DOI:10.1167/iovs.09-4008

Schwinn, M.K., Gonzalez, J.M. Jr., Gabelt, B.T., Sheibani, N., Kaufman, P.L., Peters, D.M. (2010). Heparin II domain of fibronectin mediates contractility through an alpha4beta1 co-signaling pathway. Experimental Cell Research, 316(9), 1500-1512.
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View publication via DOI: DOI:10.1016/j.yexcr.2010.03.010

Kiland, J.A., Gabelt, B.T., Tezel, G., Lutjen-Drecoll, E., & Kaufman, P.L. (2009). Effect of the age cross-link breaker alagebrium on anterior segment physiology, morphology, and ocular age and rage. Transactions of the American Ophthalmological Society, 107, 146-158.

Tian, B., Gabelt, B.T., Geiger, B., & Kaufman, P.L. (2009). The role of the actomyosin system in regulating trabecular fluid outflow. Experimental Eye Research, 88(4), 713-717.
View publication via DOI: DOI:10.1016/j.exer.2008.08.008

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.
View publication via DOI: DOI:10.1016/j.exer.2008.01.022

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.
View publication via DOI: DOI:10.1016/j.exer.2007.10.007

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].
View publication via DOI: DOI:10.1016/j.exer.2008.08.008

Croft, M.A., McDonald, J.P., James, R.J., Heatley, G.A., Lin, T.L., Lutjen-Drecoll, E., & Kaufman, P.L. (2008). Surgical intervention and accommodative responses, I: Centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages. Investigative Ophthalmology and Visual Science, 49(12), 5484-5494.
View publication via DOI: DOI:10.1167/iovs.08-1916

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.
View publication via DOI: DOI:10.1080/02713680701397104

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.
View publication via DOI: DOI:10.1016/j.exer.2006.12.01

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.
View publication via DOI: DOI:10.1016/j.exer.2006.09.013

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.
View publication via DOI: DOI:10.1167/iovs.04-1524

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.
View publication via DOI: DOI:10.1016/j.exer.2005.06.017

Tian, B., Hu, Y., Gabelt, B.T., & Kaufman, P.L. (2006). Factors affecting outflow facility calculations. Experimental Eye Research, 83(6), 1515-1520.
View publication via DOI: DOI:10.1016/j.exer.2006.08.008

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.
View publication via DOI: DOI:10.1167/iovs.05-0626

Gabelt, B.T., Hu, Y., Vittitow, J.L., Rasmussen, C.A., Grosheva, I., Bershadsky, A.D., Geiger, B., Borras, 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.
View publication via DOI: DOI:10.1016/j.exer.2005.12.002

Grosheva, I., Vittitow, J.L., Goichberg, I., Borras, 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.
View publication via DOI: DOI:10.1016/j.exer.2006.01.006

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.
View publication via DOI: DOI:10.1016/j.exer.2005.10.021

May, C.A., Gottanka, J., Kaufman, P.L., Lutjen-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.
View publication via DOI: DOI:10.1016/j.exer.2005.11.003

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.
View publication via DOI: DOI:10.1016/j.exer.2005.12.004

Gabelt, B.T, & Kaufman, P.L. (2005). Changes in aqueous humor dynamics with age and glaucoma. Prog. Re.t Eye Res., 24, 612-637.
View publication via DOI: DOI:10.1016/j.preteyeres.2004.10.003

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.
View publication via DOI: DOI:10.1016/j.exer.2005.04.010

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.
View publication via DOI: DOI:10.1007/s11357-005-4005-8

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.
View publication via DOI: DOI:10.1167/iovs.02-0569

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.
View publication via DOI: DOI:10.1364/JOSAA.19.000144

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.
View publication via DOI: DOI:10.1364/JOSAA.18.000265

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.
View publication via DOI: DOI:10.1016/S0161-6420(00)00039-7

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., Lutjen-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.

Lutjen-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.
View publication via DOI: DOI:10.1016/0014-4835(88)90070-X

Lutjen-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.
View publication via DOI: DOI:10.1016/S0014-4835(87)80153-7

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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