Evaluation of a Retina with a Subretinal Microphotodiode Array
Machelle Pardue, PhD
(2001 - 2004)

OBJECTIVES: Currently there are no effective treatment strategies to restore visual sensitivity to patients blinded by photoreceptor degeneration. One possible treatment under development for these patients is the wayfinding microphotodiode array (MPA). This small silicon wafer is covered with semi-conductor based microphotodiodes that produce electrical signals in response to light, much like the native photoreceptors. The fundamental idea is that implantation of this device into the wayfinding space will bring it into contact with cells of the inner retina, which will be activated by the electrical output of the MPA. Once these cells are activated, it is expected that the visual pathway will propagate the signal centrally like any other visual response. A key question in the development of the wayfinding implant concerns the effect(s) the implant may have on the inner retina and the nature of the implant-retina interface. With respect to these questions, we observed a general disorganization of the inner nuclear layer cells, that may be indicative of a loss of certain cell types or their cell-specific connections. In addition, we have noted the presence of a thin layer of cells surrounding the implant, which may physically interfere with the development of a stable interface between the implant and retinal neurons. The purpose of the present project is to define the time course and nature of these inner retinal changes, which will be instrumental in the development of this approach. RESEARCH PLAN: Under support from the VA Rehabilitation Research and Development program, we have established a cat model with which to evaluate key features of the wayfinding implant. Using this feline model in which these initial observation were made, additional cats will be implanted and then the eyes enucleated at specific time points to identify the cells surrounding the implant. METHODS: Cats will be implanted with an IrOx-based artificial silicon retina and followed for 2, 4, 6, 8, and 12 weeks post-op. The eyes will be enucleated and processed for immunocytochemistry. In doing so, we will take advantage of an improved sectioning technique which provides for the implanted retina to be sectioned with the implant in situ, i.e., without first removing the implant as has been done in the past. Various antibodies to specific microglia and other immunological proteins will be used to identify the cells surrounding the implanted device. CLINICAL RELEVANCE: This work will further our understanding of how the implant interfaces the native retina, thus providing value information for the advancement of this technology to be used to treat blindness resulting from photoreceptor degeneration.