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Bex P.J.,Schepens Eye Research Institute
Journal of Vision | Year: 2010

The perception of object structure in the natural environment is remarkably stable under large variation in image size and projection, especially given our insensitivity to spatial position outside the fovea. Sensitivity to periodic spatial distortions that were introduced into one quadrant of gray-scale natural images was measured in a 4AFC task. Observers were able to detect the presence of distortions in unfamiliar images even though they did not significantly affect the amplitude spectrum. Sensitivity depended on the spatial period of the distortion and on the image structure at the location of the distortion. The results suggest that the detection of distortion involves decisions made in the late stages of image perception and is based on an expectation of the typical structure of natural scenes. © ARVO.

Gipson I.K.,Schepens Eye Research Institute
Investigative Ophthalmology and Visual Science | Year: 2013

Aging of the ocular surface and corneal tissues, major components of the visual system, causes major eye disease and results in substantial cost in medical and social terms. These diseases include the highly prevalent dry eye disease that affects the ocular surface and its glands, leading to tear film alterations, discomfort, and decreased vision. Studies show that 14.4% of the population in the United States older than 50 years have dry eye disease and demonstrate that it is particularly prevalent among women. Annual medical costs per patient with dry eye in the United States are estimated at $783 per year, with an overall medical cost adjusted to prevalence of $3.84 billion per year. Societal costs, which include loss of productivity, are estimated per patient at $11,302 per year, with overall costs adjusted to prevalence of $55.4 billion per year. Because there are few effective treatments for the disease, more research on its etiology and mechanisms is warranted and needed. Increased public education about risk factors for the disease is also required. Another major age-related eye disease of the cornea that leads to vision impairment and potentially blindness if left untreated is Fuchs' endothelial corneal dystrophy. This disease leads to loss of the endothelial cells on the internal side of the cornea that are responsible for keeping the cornea in the proper hydration state to ensure its transparency to light. The mechanism of cell loss is unknown, and the only treatment available to date is surgical transplantation of the cornea or inner part of the cornea. These medically costly procedures require donor corneas, eye banking, and medical follow-up, with accrued costs. Fuchs' endothelial corneal dystrophy is a major cause of corneal transplantation in the United States; therefore, research support is needed to determine the mechanism of this age-related disease, to develop medical, nonsurgical methods for treatment. © The Association for Research in Vision and Ophthalmology, Inc.

Joyce N.C.,Schepens Eye Research Institute
Experimental Eye Research | Year: 2012

The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic "pump" functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the invivo induction of transient corneal endothelial cell division or the invitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new treatments to restore corneal clarity. © 2011 Elsevier Ltd.

Dartt D.A.,Schepens Eye Research Institute
Ocular Surface | Year: 2011

Lipocalins are a family of diverse low molecular weight proteins that act extracellularly. They use multiple recognition properties that include 1) ligand binding to small hydrophobic molecules, 2) macromolecular complexation with other soluble macromolecules, and 3) binding to specific cell surface receptors to deliver cargo. Tear lipocalin (TLC) is a major protein in tears and has a large ligand-binding cavity that allows the lipocalin to bind an extensive and diverse set of lipophilic molecules. TLC can also bind to macromolecules, including the tear proteins lactoferin and lysozyme. The receptor to which TLC binds is termed tear lipocalin-interacting membrane receptor (LIMR). LIMR appears to work by endocytosis. TLC has a variety of suggested functions in tears, including regulation of tear viscosity, binding and release of lipids, endonuclease inactivation of viral DNA, binding of microbial siderophores (iron chelators used to deliver essential iron to bacteria), serving as a biomarker for dry eye, and possessing anti-inflammatory activity. Additional research is warranted to determine the actual functions of TLC in tears and the presence of its receptor on the ocular surface. ©2011 Ethis Communications, Inc.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 233.24K | Year: 2015

DESCRIPTION provided by applicant Preclinical evaluation of treatment strategies for retinal neurodegenerative diseases is highly dependent on mouse models Classical methods to assess the visual function of animals such as electroretinogram ERG which measures electrical responses in the retina do not address connections between the eye and brain or visual perception by the visual system This often raises concerns regarding the functional relevance of the therapeutic benefit Difficulty in assessing visual perception and related behavior in mice and rats largely due to their subtle visual behavior cues and the lack of adequate measuring devices presents a critical barrier to the application of mouse models for evaluating treatment efficacy of new drugs and for scaling up for behavior phenotyping to screen genetic vision defects Pupillary light reflex PLR and optokinetic reflex OKR tests are useful methods in clinics for assessing human visual responses and perception However such tests have been difficult to conduct in rodents because current rodent visual testing methods or devices either do not allow accurate quantitative assessment for PLR or OKR or use subjective measures to score visual responses To address these challenges we propose to advance the technology by designing an easy to use automated platform that employs an eye pupil tracking device equipped with a computer vision system chiefly the interactive tracking system for unambiguous objective scoring of visual responses Our proposed new device will allow real time quantitative and accurate assessment of rodent visual function including light responses visual acuity and contrast sensitivity The novelty of our system also lies in that it does not require complicated calibration procedures needed in commonly used human eye tracking Rather than precisely measuring the extent of eye turning or orientation we propose to detect the signature eye movement in accordance with the speed and direction of visual stimuli The system will be validated using normal wildtype mice and mouse models of retinal neurodegeneration known to develop visual behavior changes in the parameters mentioned above Although rodent eye tracking has been investigated before this proposed visual assessment system would be the first commercially viable product that uses an eye pupil tracking device to automatically assess visual perception in rodents The combined PLR and OKR tests and vastly simplified and automated quantification methods will also provide the first scalable behavior platform for phenotyping and drug discovery in the vision research area In the future this technology has the potential of being expanded to measure responses from various visual stimuli This may translate into broader applications for evaluating brain diseases that afflict the visual pathways This platform for mouse visual behavior assessment will therefore greatly facilitate drug discovery and development aimed at preventing and slowing vision loss or restoring sight helping to combat devastating blinding conditions such as age related macular degeneration AMD and glaucoma PUBLIC HEALTH RELEVANCE The objective of the current proposal is to design and develop an automated system for the measure of rodent mice and rats light response visual acuity and contrast sensitivity The system will apply human eye pupil tracking techniques for objective and unambiguous evaluation of light response and visual perception This platform will provide a powerful tool for phenotypic studies as well as for discovery of new drugs that can prevent or restore sight caused by blinding conditions such as age related macular degeneration and glaucoma

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