Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

Retinal ganglion cells (RGCs) undergo continued maturation after birth. RGC development can be influenced by light, but for most RGCs this requires the development of functional retinal circuits that occurs up to 2 weeks after birth. A subpopulation of RGCs express melanopsin (MRGCs) making them intrinsically photosensitive at birth. I hypothesized that this intrinsic photosensitivity could affect the morphology of MRGCs during the postnatal (PN) developmental period (PN 3 to adult). I took advantage of the Clomeleon-expressing transgenic mouse line that, combined with melanopsin immunohistochemistry, allowed for the systematic identification of the M2 MRGC at different PN periods. The pattern of development of the M2 MRGC, characterized through the analysis of 6 morphological parameters, was similar to that described for other types of RGCs. Thus, despite being intrinsically photosensitive, M2 MRGCs did not show substantial developmental differences from other RGC types

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A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

Despite their undisputed importance to embryonic growth, the role of mRNA transport proteins in the developing visual system has been widely uncharacterized. Through RNA interference, this study aims to discover the function of Staufen 2 (Stau2), an mRNA transport protein, in chick eye development. When Stau2-miRNA was electroporated into the E1.5 primary optic vesicle, two days later they exhibited a reduction of eye size by 47%, whereas control miRNA did not significantly change eye size. TUNEL, β-III tubulin and BrdU staining were used to analyze the retinal apoptotic, differentiation and proliferative levels respectively, in response to Stau2 knockdown. These data suggest that the small eye is a result of a decrease in proliferation, and not cell death or pre-mature differentiation. Rescue experiments were done with each of the three Stau2 isoforms and confirmed both the direct effect of Stau2-miRNA and the involvement of these isoforms in eye development.

Despite their undisputed importance to embryonic growth, the role of mRNA transport proteins in the developing visual system has been widely uncharacterized. Through RNA interference, this study aims to discover the function of Staufen 2 (Stau2), an mRNA transport protein, in chick eye development. When Stau2-miRNA was electroporated into the E1.5 primary optic vesicle, two days later they exhibited a reduction of eye size by 47%, whereas control miRNA did not significantly change eye size. TUNEL, β-III tubulin and BrdU staining were used to analyze the retinal apoptotic, differentiation and proliferative levels respectively, in response to Stau2 knockdown. These data suggest that the small eye is a result of a decrease in proliferation, and not cell death or pre-mature differentiation. Rescue experiments were done with each of the three Stau2 isoforms and confirmed both the direct effect of Stau2-miRNA and the involvement of these isoforms in eye development.

Electrical stimulation of retinal neurons is known to elicit visual sensations. When applied to the retina in a spatial pattern, electrical stimulation may be capable of providing rudimentary patterned vision that may be of benefit to sufferers of degenerative retinal disorders. No such device has yet been devised to provide for chronic study of the psychophysical perceptions elicited from a prosthesis for retinal stimulation. In this study, steps towards achieving this goal have been successfully carried out. Foregoing research was reviewed such that appropriate stimulation parameters were incorporated in the design of a 100 stimulation channel, complimentary metal oxide semiconductor (CMOS) integrated circuit, small enough in size so as to be capable of being implanted within the ocular anatomy or surrounding orbit. The device, and its associated external hardware and software were designed, modeled, fabricated, and interfaced with stimulating electrodes in acute testing in a highorder mammal (Ovis aries) so as to assess the capabilities of the device to elicit cortical potentials as a direct result of stimulation of the neural retina. Testing was performed under conditions similar to those anticipated in chronic in-situ configurations wherein radio-frequency telemetry was used to deliver power and configuration parameters to the device thus avoiding the passage of wires through tissue in order to communicate to the implant circuit. The results of the testing indicate that the circuit is indeed capable of eliciting physiological responses in the animal and evidence is present that these responses could be elicited in patterned form. Further work undertaken includes the development of surgical methods for implantation, and application of the prosthesis circuit in functional electronic stimulation.