Advisory Committee Chair
Paul D Gamlin
Advisory Committee Members
Karen L Gamble
Thomas T Norton
Lawrence C Sincich
Christianne E Strang
Document Type
Dissertation
Date of Award
2022
Degree Name by School
Doctor of Philosophy (PhD) School of Optometry
Abstract
This project was conducted in Old World monkeys and focused on characterization of the intrinsically photosensitive retinal ganglion cells (ipRGCs) as they pertain to the pupillary light reflex, as well as on the neuroanatomical and electrophysiological characterization of the suprachiasmatic nucleus (SCN) of the hypothalamus as it pertains to circadian rhythms. A custom antibody was developed against the human melanopsin gene. We validated the antibody using western blot and immunohistochemistry. The functional role of ipRGCs in driving pupillary responses was investigated through immunotoxin-induced ablation in Rhesus macaques with the antibody conjugated to saporin. As hypothesized, the pupillary light reflex and post-illumination pupil responses were greatly reduced or eliminated. We subsequently focused on identifying anatomical subregions in the SCN of Old World monkeys by using immunohistochemistry. We identified a subgroup of Calbindin-D28k cells in the core of the SCN that is similar to a region in hamsters that is critical for controlling circadian rhythms. We found vasoactive intestinal peptide (VIP) and gastrin releasing peptide (GRP) positive cells in the ventrolateral SCN whereas the arginine vasopression (AVP) and substance P (SP) labeling were located in the dorsomedial SCN. iv Finally, we investigated the physiological response properties of the photically-driven neurons within the SCN. Results were obtained from six neurons, five that showed light-activated activity and one of which showed light-suppressed activity. All cells displayed transient and sustained responses to light as well as a post-illumination response at higher light intensities. The threshold light intensity required to activate the sustained response of SCN neurons was approximately one log unit higher than that required to drive the sustained pupil constriction. The receptive fields of the SCN neurons included both the contralateral and ipsilateral hemifields - presumably a result of SCN interconnections. This study has identified the role played by ipRGCs in primate pupil responses as well as showing that the primate SCN can be subdivided into subregions using appropriate immunohistochemical markers. Isolating single-units in the macaque SCN was feasible but hard to implement due to a number of technical issues identified by this project. Nevertheless, to my knowledge, this is the first report, albeit limited, on the electrophysiological characteristics of SCN neurons in the macaque monkey.
Recommended Citation
Chang, Kevin Q., "Intrinsically-Photosensitive Retinal Ganglion Cells and Their Functional Roles" (2022). All ETDs from UAB. 197.
https://digitalcommons.library.uab.edu/etd-collection/197