Extra-lenticular aspects of accommodation and presbyopia

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DESCRIPTION (provided by applicant): Human accommodative amplitude (the ability of the eye to focus on near objects) declines progressively, beginning in the second decade of life and perhaps earlier, and is completely gone by age 50-55 years.5 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.6 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,7 the accommodative apparatus of the rhesus monkey eye is very similar to that of the human eye.8-10 Rhesus accommodation declines on a relative time scale that is essentially identical to that of the human.10 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.11, 12 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.11, 12 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,"6, 13-19 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). Our goal is two fold: 1) To investigate and define the role of extralenticular components of the accommodative apparatus in age-related ciliary muscle immobility, which may be crucial in preserving forward ciliary body (FCB) movement and in enabling the function of the next-generation accommodating IOLs; and 2) To determine the predictive relevance of the monkey for the human situation. We seek to develop a more complete understanding of the mechanism of presbyopia in primates and to identify a biological target for human therapy, but not necessarily to identify a therapeutic surgical procedure for that target in the human eye. 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).