Date on Master's Thesis/Doctoral Dissertation

8-2013

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Committee Chair

McCall, Maureen Ann

Author's Keywords

Retinitis pigmentosa; Retina; Prosthesis; Photovoltaic array

Subject

Eyes, Artificial; Retina--Surgery; Retina

Abstract

With increasingly successful clinical trials, the use of prosthetic devices to replace the function of photoreceptors has now become a viable option to treat degenerative diseases of the retina, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Using prosthetics, patients have demonstrated the ability to read large text, recognize small objects, and navigate. While promising, this represents coarse visual function, with the highest visual acuity equivalent to 20/560, still below the legal definition of blindness, 20/200. To investigate the benefit of more sophisticated designs, I implanted two types of photovoltaic prosthetic devices in two models of RP, Tg S334ter-3 and Tg P23H-1 rats. The performance of a new bipolar photovoltaic array (bPVA) design with local ground returns was compared to a monopolar photovoltaic array (mPVA) with a single ground return. Regardless of implant design, stimulation parameters at threshold were at least 1.5 orders of magnitude below safety limits. Age and duration of implantation had no significant effect on stimulation thresholds while threshold increased inversely to pixel size. In addition to treating the symptoms of these diseases, a better understanding of the functional consequences of degeneration will help guide future treatment strategies. I examined changes in visual function in the retina and the superior colliculus (SC). I found profound changes in visual function in both models. First, the ON pathway is preferentially lost due to a shift from equal numbers of ON and OFF ganglion cells in the retina and ON dominated responses in the SC to OFF dominated responses in both. In the Tg P23H-1 rat, this shift is progressive with age, while in the Tg S334ter-3 this shift is evident early in life. In late stages of the disease, there is little response from the ON pathway. In animals implanted with bPVA devices, there was a significant change in the response based on the location of the prosthesis, with a preservation of the ON pathway in areas directly under the influence of the prosthesis. Either the presence of the device or basal electrical activity may induce a trophic influence that attenuates this change in visual function.

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