UW Eye Research Institute Rapid Response Initiative Awards (Second application cycle, 2009)
Project Title: The BigEye Mouse: Genetic Basis
Principal Investigator
Christopher Bradfield (Oncology) |
Collaborator(s)
Dick Dubielzig (Pathobiological Sciences, Vet Med)
Norman Drinkwater (Oncology)
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Project Abstract: The BigEye mouse is a model of posterior polymorphous dystrophy (PPD). Retinal abnormalities are also associated with BigEye. Human PPD is an autosomal dominant disorder characterized by abnormal growth of corneal endothelial cells. Human PPD, like many human eye disorders, can be linked to more than one chromosomal locus. One PPD locus has been mapped to Chromosome 20, but a specific gene mutation has not yet been identified. The BigEye mouse exhibits corneal endothelial cell abnormalities similar to those observed in human PPD. Like its human counterpart, the mouse BigEye mutation is inherited in an autosomal dominant manner. To date, we have characterized the BigEye ocular phenotype and localized the BigEye mutation to a region of mouse Chromosome 2 which corresponds closely to the region on human Chromosome 20 implicated in human PPD. Thus, we believe that the BigEye mutation is the mouse counterpart of human PPD linked to Chromosome 20. In order to understand the molecular basis for the ocular phenotypes observed in the affected animals, we now propose a number of approaches to identify the gene mutation responsible for BigEye.
Project Title:3D Analysis of Spectral Domain OCT Images in Feline Models of Optic Neuropathies
Principal Investigator
Gillian McLellan
(Ophthalmology and Visual Sciences, Surgical Sciences – Vet Med) |
Collaborator(s)
James VerHoeve, Carol Rasmussen (Ophthalmology & Visual Sciences)
Ian Duncan, Dick Dubielzig (Vet Med)
Mona Garvin, Milan Sonka, Michael Abràmoff (Iowa Institute for Biomedical Imaging, Univ. of Iowa)
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Project Abstract: Two unique feline models for important human optic nerve diseases (glaucoma and demyelinating disease) are currently undergoing structural and functional characterization at UW-Madison. We are able to obtain high quality 3D images of the cat retina in vivo using spectral-domain optical coherence tomography (SD-OCT). However, our efforts to quantify structural changes in the inner retina of affected cats are currently hampered by a failure of proprietary software to reliably and accurately recognize and segment retinal layers in OCT images of the feline retina. The proposed study will forge new collaborations between researchers in the Schools of Medicine and Public Health and Veterinary Medicine at University of Wisconsin-Madison and researchers from the Iowa Institute for Biomedical Imaging at the University of Iowa. Our collaborative efforts will address the following specific aims:
1) Generate and refine an algorithm for segmenting retinal layers in cats from 3D, SD-OCT images. 2) Derive global and focal structural indices, such as thickness and texture, for each retina/layer in normal cat eyes and in eyes with impairment of vision resulting from glaucoma and demyelinating optic neuropathy. 3) Obtain histopathologic correlates to validate the structural indices derived under Aims 1 & 2 in the same subsets of cats. Once completed, our studies will validate 3D image analysis of SD-OCT of the retinal layers as a reliable and reproducible technique in the longitudinal assessment of the status of retinal damage in animal models, and support the technique's application in human patients.
Project Title: Hydrogel Devices that Promote Cell Survival during Keratoplasty
Principal Investigator
Neal Barney
(Ophthalmology & Visual Sciences) |
Collaborator(s)
William Murphy (Biomedical Engineering)
Javeed Shaikh Mohammed (Biomedical Engineering)
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Project Abstract:The cornea is the outer, clear, window of the eye. Swelling of the cornea reduces visual acuity by causing scattering of light rays that would otherwise be properly bent to a focus onto the light receptor layer - the retina, in the back of the eye. Excess swelling, or increased water within the substance of the cornea is pumped out by a single layer of endothelial cells. These line the inside back of the cornea. If these cells diminish in number or lose function below a threshold, the cornea will swell. Cornea swelling is a leading cause for the performance of cornea transplantation. Cornea transplantation involves recovery of donor tissue, excision of the patient's own cornea, and replacement with the donor tissue which is secured by sutures. Recent changes have focused on replacing just the posterior layer of the cornea containing the endothelial cells for cornea conditions leading to swelling. A further modification of the this posterior replacement technique transplants only the endothelial cells on their underlying basement membrane. Biogel technology may be used to protect these cells during recovery and transplantation and enable this procedure. Biogels may vary in thickness, composition, ability to dissolve, and are compatible with human tissues. We propose the development of a biogel based device which will facilitate recovery of just the basement membrane and endothelial cells from donor corneas and serve as carrier into the recipient for the transplanted tissue. This would significantly reduce wasted tissue and cell loss and improve outcome.
Project Title: Using Eye Movement to Study Participants’ Reading and Motor Performance
Principal Investigator
Paula Wolfe (Curriculum & Instruction) |
Collaborator(s)
Andrea Mason (Kinesiology) |
Project Abstract:This collaborative research uses human eye movements to study the two-stage information processing during cognitive reading and motor performance. While originally proposed to account for eye movements during reading performance, the two-stage information processing theory will be used to interpret data in both the cognitive and motor tasks. For reading performance, stage one processing involves a simple literal interpretation of the text, characterized by briefer fixations and fewer intersentential regressions. Stage two processing involves solving problems encountered with increased text complexity and is characterized by long deep-processing fixations and more inter-sentential and text-graphic regressions. For the reading task, our research will focus on participants' eye movement regression between text and pictures as they read graphic texts. During the motor task, participants will perform aiming and reach-to-grasp movements with varying levels of advance information about the nature of the task. We will investigate whether subjects use the same two-stage information processing model to solve the task: specifically when participants are not given enough information about the motor task, do they enter the first stage of information processing where fixations are numerous, brief and characterized by regressions toward the hand?