Our research into the pathophysiology of presbyopia, the age-related loss of the eye's ability to focus on near objects, has found evidence in a monkey model that the aging ciliary muscle is restricted in accommodative movement by its posterior elastic attachments. In the Parent R21 grant application, our goal is to determine the role of the posterior zonule in accommodation and presbyopia. In this supplement application (Notice number: NOT-OD-09-058) we wish to expand our investigation by determining the role of the choroid, another of the ciliary muscle's posterior elastic attachments, in restricting the accommodative movement of the ciliary muscle with age. Human accommodative amplitude (the ability of the eye to focus on near objects) declines progressively with age, beginning in the second decade of life and perhaps earlier, and is completely gone by age 50-55 years.[1] No individual appears exempt, making presbyopia (literally, """"""""old eye"""""""") the most common ocular affliction in the world. Although certainly not a blinding condition, and correctable by various optical means, presbyopia's cost in devices and lost productivity is substantial.[2] Although much useful and relevant information has been garnered from studies in living and postmortem human eyes, the invasive techniques required to answer some of the most critical questions cannot be employed in the living human. While the eyes of subprimate species either do not accommodate or accommodate by mechanisms very different from that of the human,[3] the accommodative apparatus of the rhesus monkey eye is very similar to that of the human eye.[4] [5] [6] Rhesus accommodation declines on a relative time scale that is essentially identical to that of the human.[5] Our group has utilized the rhesus monkey to contribute significant new information relevant to presbyopia pathophysiology. In this model, we have demonstrated that the ciliary body excursion during accommodation diminishes with age, probably due to an age-related decrease in elasticity of the posterior attachments.[7, 8] This restricts the degree of accommodative amplitude. We have also shown that the movement of the lens equator decreases with age, again resulting in reduced accommodative amplitude.[7, 8] Further, although histological data from excised postmortem human eyes shows the older human ciliary body at rest in an anterior/inward position, we have preliminary imaging data that suggest this may not be the case in vivo (see Preliminary Studies). Classical teaching attributes presbyopia to """"""""lenticular sclerosis,"""""""" or """"""""lens hardening,""""""""[2, 9-15] so that the lens cannot change shape, but the definitive mechanism that results in presbyopia remains elusive. In search of a way to restore some degree of accommodative amplitude, we hypothesize that age-related immobility of the muscle is due to posterior restriction. Further, if these posterior restrictions are eliminated, mobility of the muscle can be restored and facilitate the function of accommodating intraocular lenses (IOLs).

Public Health Relevance

Our goal is to determine what role the extralenticular tissues play in the pathophysiology of age- related ciliary muscle immobility in the non-human primate, and to determine whether the resulting model is relevant to human presbyopia. This may be crucial in enabling the function of next- generation intraocular lenses (IOLs).

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BDCN-T (95))
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Wujek, Jerome R
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University of Wisconsin Madison
Schools of Medicine
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Croft, Mary Ann; Heatley, Gregg; McDonald, Jared P et al. (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 Physiol Opt 36:21-32
Flügel-Koch, Cassandra M; Croft, Mary Ann; Kaufman, Paul L et al. (2016) Anteriorly located zonular fibres as a tool for fine regulation in accommodation. Ophthalmic Physiol Opt 36:13-20
Croft, Mary Ann; McDonald, Jared P; Katz, Alexander et al. (2013) Extralenticular and lenticular aspects of accommodation and presbyopia in human versus monkey eyes. Invest Ophthalmol Vis Sci 54:5035-48
Croft, Mary Ann; Nork, T Michael; McDonald, Jared P et al. (2013) Accommodative movements of the vitreous membrane, choroid, and sclera in young and presbyopic human and nonhuman primate eyes. Invest Ophthalmol Vis Sci 54:5049-58
Lütjen-Drecoll, Elke; Kaufman, Paul L; Wasielewski, Rainer et al. (2010) Morphology and accommodative function of the vitreous zonule in human and monkey eyes. Invest Ophthalmol Vis Sci 51:1554-64
Croft, Mary Ann; McDonald, Jared P; Nadkarni, Nivedita V et al. (2009) Age-related changes in centripetal ciliary body movement relative to centripetal lens movement in monkeys. Exp Eye Res 89:824-32
Wasilewski, Rainer; McDonald, Jared P; Heatley, Gregg et al. (2008) Surgical intervention and accommodative responses, II: forward ciliary body accommodative movement is facilitated by zonular attachments to the lens capsule. Invest Ophthalmol Vis Sci 49:5495-502
Croft, Mary Ann; McDonald, Jared P; James, Rebecca J et al. (2008) Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages. Invest Ophthalmol Vis Sci 49:5484-94