Age-related Macular Degeneration (AMD) is the most common cause of permanent vision loss in industrialized countries. While some risk factors are known, the ability to identify those subjects most at risk is still limited. We have shown that using advanced imaging techniques middle-aged individuals have varying amounts of early changes in the photoreceptor/Retinal Pigment Epithelium/Bruch's membrane complex. The long term goal is to detect the earliest changes related to inflammatory processes, so that targeted treatments can be devised to prolong vision and prescribed to only appropriate subjects, thereby reducing side effects for those who do not have early changes. The early damage to the human fundus that is predicted by inflammatory models will be probed with noninvasive laboratory methods to target separately Bruch's membrane/Retinal Pigment Epithelium, cone photoreceptor outer segments, and cone and rod cell bodies in the Outer Nuclear Layer. This project directly addresses Program Goals of the National Eye Institute, particularly """"""""With regard to macular degeneration, understand the molecular and biochemical bases for its different forms, improve early diagnosis."""""""" In Aim 1, we will investigate the earliest possible changes to the photoreceptors using adaptive optics imaging and high resolution OCT.
In Aim 2, we will quantify disruption to the Retinal Pigment Epithelium using polarized light imaging.
In Aim 3, we will develop and use novel fluorescence techniques to map the spatial variations in fluorophores of lipofuscin.
In Aim 4, we will further develop polarization sensitive OCT to probe inflammatory signs within and beneath the retinal pigment epithelium, as these is predicted to increase not only the thickness but also the phase retardation.
In Aim 5, we will use quantitative data and novel techniques to test models that hypothesize that inflammatory changes are a unifying concept predicting all of the age- related increase in structural markers measured in Aims 1-4. Further, we will develop new techniques that are broadly applicable for microscopy and biomedical imaging.

Public Health Relevance

Age-related Macular Degeneration is the leading cause of irreversible vision loss in industrialized countries. Using state of the art imaging and fluorescence measurements, we will characterize early changes to the photoreceptors, retinal pigment epithelium, and Bruch's membrane in the eyes of healthy adults. We will test whether the damage can be modeled as the early occurrence of an inflammatory response that differs among individuals and who could benefit from personalized treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007624-20
Application #
8288213
Study Section
Special Emphasis Panel (ZRG1-ETTN-E (92))
Program Officer
Shen, Grace L
Project Start
1987-09-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
20
Fiscal Year
2012
Total Cost
$498,321
Indirect Cost
$174,736
Name
Indiana University Bloomington
Department
Type
Schools of Optometry/Ophthalmol
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Elsner, Ann E; Chui, Toco Y P; Feng, Lei et al. (2016) Distribution differences of macular cones measured by AOSLO: Variation in slope from fovea to periphery more pronounced than differences in total cones. Vision Res :
King, Brett J; Sapoznik, Kaitlyn A; Elsner, Ann E et al. (2016) SD-OCT and Adaptive Optics Imaging of Outer Retinal Tubulation. Optom Vis Sci :
Clark, Christopher A; Elsner, Ann E; Konynenbelt, Benjamin J (2015) Eye shape using partial coherence interferometry, autorefraction, and SD-OCT. Optom Vis Sci 92:115-22
Chui, Toco Y P; VanNasdale, Dean A; Elsner, Ann E et al. (2014) The association between the foveal avascular zone and retinal thickness. Invest Ophthalmol Vis Sci 55:6870-7
Burns, Stephen A; Elsner, Ann E; Chui, Toco Y et al. (2014) In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy. Biomed Opt Express 5:961-74
VanNasdale, Dean A; Elsner, Ann E; Peabody, Todd D et al. (2014) Henle fiber layer phase retardation changes associated with age-related macular degeneration. Invest Ophthalmol Vis Sci 56:284-90
Cense, Barry; Wang, Qiang; Lee, Sangyeol et al. (2013) Henle fiber layer phase retardation measured with polarization-sensitive optical coherence tomography. Biomed Opt Express 4:2296-306
Chui, Toco Y P; Gast, Thomas J; Burns, Stephen A (2013) Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 54:7115-24
Elsner, Ann E; Petrig, Benno L; Papay, Joel A et al. (2013) Fixation stability and scotoma mapping for patients with low vision. Optom Vis Sci 90:164-73
Chui, Toco Y P; Song, Hongxin; Clark, Christopher A et al. (2012) Cone photoreceptor packing density and the outer nuclear layer thickness in healthy subjects. Invest Ophthalmol Vis Sci 53:3545-53

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