We seek to continue and advance our group's study of human accommodative amplitude (the maximum ability of the eye to focus on near objects) and accommodative loss (presbyopia, literally old eye) the most common ocular affliction in the world. Through our group's recent research in the monkey model, we have made the significant discovery of the existence of new extralenticular-zonular structures (PVZ INS-LE strands), which are linked to accommodation. In particular, we hypothesize that these structures may act as a strut to the posterior lens equator during accommodation and thereby facilitate accommodative lens thickening. Likewise, preliminary studies in the monkey eye suggest cistern-like structures in the vitreous, which we hypothesize play a role in fluid exchange between the anterior and posterior segments during accommodation. Despite these novel discoveries, it is clear that aspects of accommodation and the definitive mechanisms that result in presbyopia are yet to be fully determined and studied. Likewise, we hypothesize that age-related immobility of the ciliary muscle is due to posterior restriction. We postulate that, if cerain posterior restrictions are eliminated, mobility of the muscle can be restored and can facilitate th function of accommodating intraocular lenses (IOLs). The goals of our proposed research are: 1) To investigate and define the new players in the posterior restriction of the ciliary muscle, elucidation of which may be crucial in preserving forward ciliary body (FCB) movement and in enabling the function of the next-generation accommodating IOLs; 2) Determine the posterior extent of choroid/retina accommodative movement (i e., optic nerve region) with implications for accommodative mechanism and biomechanical models; 3) Define the role that the various intraocular structures (i.e., anterior hyaloid, vitreous zonule, vitreous cistern-like structure, PZ INS-LE strand, Hannover's Canal) play during accommodation and their change with age in the rhesus monkey (due to similarities to the human eye); and 4) To identify a biological target for human presbyopia therapy, albeit not necessarily a therapeutic surgical procedure for that target in the human eye. We believe the identification of, and proposed continued research of, these and associated structures will affect the understanding of how the eye accommodates earlier in life, and thereby change how we understand and treat presbyopia. The energy and excitement in our group is high, based upon our recent progress and the promises they hold for those with presbyopia.

Public Health Relevance

Our goal is to determine what role extralenticular tissues play in accommodation and in the pathophysiology of progressive age-related ciliary muscle immobility, in humans and nonhuman primates, and thus ultimately in human presbyopia. Delineating, understanding, and manipulating these relationships may also be crucial in enabling the functionality of next generation accommodating intraocular lenses (IOLs).

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY025359-04
Application #
9614987
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Araj, Houmam H
Project Start
2016-01-01
Project End
2019-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Croft, Mary Ann; Lütjen-Drecoll, Elke; Kaufman, Paul L (2017) Age-related posterior ciliary muscle restriction - A link between trabecular meshwork and optic nerve head pathophysiology. Exp Eye Res 158:187-189
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