Diseases in the nervous system alter neural circuitry and thus affect the neural code. Retinitis pigmentosa (RP), for example, is an inherited blinding disease that causes the degeneration of rod photoreceptors (Fariss, Li, and Milam 2000; Fei 2002; Strettoi and Pignatelli 2000). In RP, issues in the rod light receptors affect visual processing because they are the first step in absorbing photons of light to create electrochemical messages. Greater progression of RP begins secondary deformities and loss of cells in most of the remaining cell classes in the retina (Phillips, Otteson, and Sherry 2010). In addition, synapses and gap junctions – the communication networks of neurons – eventually rewire (Cuenca et al. 2004; Jones et al. 2003; Lu et al. 2013; Lund et al. 1998; Marc and Jones 2003; Pfeiffer et al. 2020). While the cellular anatomy of RP is eloquently described in literature, how the retina behaves in the context of this disease is not as clear. Furthermore, there is also room to improve genetic cures for RP by focusing on its secondary morphological changes.
0.1 Retinal Communication Performance During Disease
Our first goal is to search for functional changes in the neural code during degeneration. If much of the retina’s function is maintained with disease, then therapies may be able to prevent retinal damage. To put it more precisely, we want to characterize retinal coding so we can determine whether genetic, prosthetic, or optogenetic therapies would be able to prevent further vision decline in RP patients. Thus, these functional assay techniques of information theory and spike train consistency can provide baseline assessments of treatments.
0.2 Transcriptomic Profile of RP in Retinal Bipolar Cells
The second problem we seek to answer is in exploring the genetic mechanisms that can halt secondary retinal damage. Specifically, the bipolar cells which link the outer retina to the inner retina (Euler et al. 2014) provide a potential cell class for treatment. These cells interact with all classes of retinal cells and modulate parallel channels of visual processing. Reviving the photoreceptors by themselves does not guarantee that interneuron interactions will be maintained (Pfeiffer et al. 2020), so correcting bipolar cell connections would lead to more effective therapies. To take a wider view, if we try to reduce secondary deformities in RP – which include the synapses between bipolar cells with rods, cones, amacrine cells, and retinal ganglion cells – retinal communication and thus vision may improve.
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