Disruptions of visual processing by the inner retina accompanying photoreceptor degenerations

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Background

Until quite recently, studies of hereditary retinal degenerations naturally have focused primarily on the most obvious hallmark of these diseases: the dysfunction and eventual death of the classical photoreceptors (rods & cones). The morphologic and functional integrity of the remaining inner (neural) retina has been felt to be largely preserved. However, an increasing number of investigations over the past decade or two have drawn attention to additional disruptions of visual processing by the complex neural circuits of the inner retina. This Research Topic will summarize our most up-to-date understanding of the range of alterations of inner retinal structure and function that accompany a variety of animal models of retinal degeneration studied to date, with particular emphasis on aberrant electrophysiology.

One section will summarize morphologic changes in retinal cells and circuits other than photoreceptors. A central section will describe one common and prominent abnormality: elevated levels of spontaneous (“background”) activity that occur in multiple cell types at several levels and parallel pathways of visual processing. This hyperactivity is often oscillatory in nature, but variations in its characteristics occur among different animal models of retinal degeneration. Several distinct circuits and intertwining mechanisms – both synaptic and non-synaptic – have been proposed to underlie this spontaneous activity. These will be reviewed and contrasted, as will its potential impact on downstream CNS targets. A third section of this Research Topic will review aberrations of light responses among inner retinal neurons, particularly the ganglion cells (RGCs), including contrasting findings among different retinal degeneration models. A particularly intriguing feature to be treated is the dependence of the changes in both spontaneous and light-evoked activity on the age of disease onset, and the interactions of degenerative processes with the normal developmental course of retinal circuit maturation. Finally, we will consider the ultimate implications of abnormal visual signal processing by the retina for visual perception and behavior, clinical testing, and the potential to improve current sight-restoring treatments and to develop new, innovative therapies.

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