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Photopotentiation of Ganglion Cell Photoreceptors and Pupillary Light Responses

Yuhas, Phillip Thomas
http://orcid.org/0000-0002-5956-4957
http://rave.ohiolink.edu/etdc/view?acc_num=osu1562081394270483

Abstract Details

2019, Doctor of Philosophy, Ohio State University, Vision Science.
A rare subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin that enables them to capture light and signal downstream targets independently from rods and cones. These blue-light sensitive, sluggish neurons act as irradiance detectors, signaling environmental light levels to brain centers that control aspects of non-image-forming vision, including the pupillary light response. Under physiological conditions, these cells are not isolated from external modulators. The overall objective of this dissertation was to quantify how ipRGC function can be influenced by retinal neuromodulators and then explore conditions in vivo in which ipRGC modulation may occur or be altered. First, multielectrode array recordings were obtained from rat retinas in vitro to determine whether dopamine D1 receptor agonists and antagonists affect light-evoked spiking in RGCs, including ipRGCs. The D1 receptor agonist, SKF 38393, significantly increased the spiking of synaptically intact ipRGCs and ON RGCs in response to a bright, flickering blue light, compared to baseline. A delayed SKF 38393-mediated enhancement was observed for ipRGCs that were pharmacologically isolated from glutamatergic input. Exposure to a D1 receptor antagonist, SCH 23390, did not significantly alter light-evoked spiking in pharmacologically isolated ipRGCs. Second, I analyzed human pupillary light responses to different flickering light stimuli in order to determine whether prior light exposure influences the contribution of ipRGCs to the pupillary light reflex. I found that a bright stimulus that flickered between darkness and red and blue lights was able to progressively increase the amount of sustained pupil constriction that occurred after the offset of each light. This aspect of the pupillary light response is primarily driven by intrinsic melanopsin-related photoresponses of ipRGCs. More gradual photopotentiation was observed in the pupillary light responses to a bright, red flickering stimulus and to three dim flickering stimuli of various spectral compositions (red, blue, and red-blue alternating). Initial pulses of all these stimuli appeared to be below threshold necessary for melanopsin activation in dark adapted ipRGCs. However, these results support the premise that these relatively dim stimuli can activate melanopsin with repeated light exposures, indicating that ipRGCs have a larger dynamic range of light sensitivity than previously thought. Third, I investigated the pupillary light responses to red and blue flickering lights in human subjects suffering from post-traumatic brain injury (TBI) photophobia and compared the results to matched controls. The mean pupil responses did not differ between these two groups, but there was significantly more variability in the TBI group. This finding suggests that, although ipRGC light sensitivity does not uniformly change after a TBI, there may be heterogeneous effects of the injury on ipRGC function. In addition, I found that clinical observers cannot identify light-aversion behavior elicited by flickering red and blue lights in photophobic TBI subjects. The need remains for an objective test for detecting photophobia and monitoring its progression in individuals with TBI.
Andrew Hartwick, OD, PhD (Advisor)
Angela Brown, PhD (Committee Member)
Dean VanNasdale, OD, PhD (Committee Member)
Jordan Renna, PhD (Committee Member)
266 p.
Neurobiology; Ophthalmology
Intrinsically photosensitive retinal ganglion cells; Dopamine; Pupil; Traumatic Brain Injury

Recommended Citations

Citations

  • Yuhas, P. T. (2019). Photopotentiation of Ganglion Cell Photoreceptors and Pupillary Light Responses [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1562081394270483

    APA Style (7th edition)

  • Yuhas, Phillip. Photopotentiation of Ganglion Cell Photoreceptors and Pupillary Light Responses. 2019. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1562081394270483.

    MLA Style (8th edition)

  • Yuhas, Phillip. "Photopotentiation of Ganglion Cell Photoreceptors and Pupillary Light Responses." Doctoral dissertation, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1562081394270483

    Chicago Manual of Style (17th edition)

osu1562081394270483
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This open access ETD is published by The Ohio State University and OhioLINK.