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AN INVESTIGATION OF DARK ADAPTATION: THE ROLE OF METABOLISM
AND ALTERNATIVE ROD PATHWAYS IN SHAPING VISUAL SENSITIVITY
FOLLOWING BRIGHT LIGHT
by
Kiyoharu Joshua Miyagishima
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(SYSTEMS BIOLOGY AND DISEASE)
August 2010
Copyright 2010 Kiyoharu Joshua Miyagishima
Object Description
| Title | An investigation of dark adaptation: the role of metabolism and alternative rod pathways in shaping visual sensitivity following bright light |
| Author | Miyagishima, Kiyoharu Joshua |
| Author email | k.j.miyagishima@gmail.com; kmiyagis@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Systems Biology & Disease |
| School | Keck School of Medicine |
| Date defended/completed | 2010-04-29 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-07-23 |
| Advisor (committee chair) | Sampath, Alapakkam |
| Advisor (committee member) |
Chen, Jeannie Chow, Robert Craft, Cheryl Grzywacz, Norberto |
| Abstract | The visual system operates in over ten orders of magnitude of light intensity and smoothly transitions from darkness to light using a two-photoreceptor system consisting of retinal rods and cones. As in all sensory systems, adaptation is essential for encoding information effectively as the mean stimulus intensity increases. In particular, photoreceptor sensitivities and the circuits that carry receptor information define the operating range of the system and must adapt to maintain sensitivity over a wide range of light intensities. Light adaptation reduces the amplification of the G-protein signaling cascade, such that the response per photon becomes smaller, and the light responses become shorter with faster decay, effectively desensitizing the cell.; Exposure to bright bleaching light also results in adaptation in a manner similar to exposures to background light that desensitizes the cell. In rods, which are more sensitive, this adaptation is long-lasting since they are slow to regain their sensitivity. The loss in sensitivity can be explained by two phenomenon, the first owing to the loss in available photopigment for photon absorption and the second resulting from residual catalytic activity of the photoproducts of bleaching. In the first study, I examined the mechanism by which rods remain responsive despite the bleaching of a majority of their pigment; I measured the steady-state sensitivity following defined extents of pigment bleaching in the mouse retina. In single cell recordings from bleached retina I show that alternative pathway that alternative rod pathways preserve and pool rod signals to improve overall sensitivity in the mesopic range. I also discuss the implications of retinal processing of rod signals for visually-guided behavior, and relate my findings with previous psychophysical studies on rod monochromat subjects.; The recovery of sensitivity requires restoration of the visual pigment that leads to quenching of phototransduction activity. This mechanism of pigment regeneration through the visual cycle is known as dark adaptation. In the second study, I focused on understanding the role played by cellular metabolism in controlling our photoreceptors ability to dark adapt, and in some situations how metabolism places limitations on the rate of recovery of sensitivity. Through simultaneous suction recordings and patch dialysis on salamander rods, I provide physiological evidence that suggests the persistence of all-trans retinal delays dark adaptation. I show that NADPH is required for the reduction and clearance of all-trans retinal, a key first step in quenching the phototransduction cascade.; The inability to dark adapt has been implicated in blinding diseases including dry AMD, and Stargardt disease, highlighting the therapeutic importance of understanding the physiological mechanisms governing dark adaptation. Together these studies have contributed to our understanding of bleaching adaptation and may lead to the development of therapeutic strategies to treat deficiencies in the visual cycle that may lead to the accumulation of retinal-related toxic byproducts. |
| Keyword | dark adaptation; bleaching adaptation; rod photoreceptor; retina pathways |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3210 |
| Rights | Miyagishima, Kiyoharu Joshua |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Miyagishima-3766 |
| Archival file | uscthesesreloadpub_Volume35/etd-Miyagishima-3766.pdf |
Description
| Title | Page 1 |
| Full text | AN INVESTIGATION OF DARK ADAPTATION: THE ROLE OF METABOLISM AND ALTERNATIVE ROD PATHWAYS IN SHAPING VISUAL SENSITIVITY FOLLOWING BRIGHT LIGHT by Kiyoharu Joshua Miyagishima A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (SYSTEMS BIOLOGY AND DISEASE) August 2010 Copyright 2010 Kiyoharu Joshua Miyagishima |
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