**1. Introduction**

Photoreceptor cells are highly specialized, terminally di fferentiated neurons that detect photons of light and transmit this information to bipolar cells in the retina. Unfortunately, their exacting structural and metabolic requirements make them very susceptible to a large number of acquired and genetic sources of injury, leading to irreversible vision loss [1]. Degenerative diseases a ffecting photoreceptor cells have multiple etiologies. For example, genetic variants in over 100 genes have been shown to cause heritable photoreceptor degeneration [2]. However, photoreceptor degeneration can also be immune mediated, as in the case of autoimmune retinopathy (AIR), where circulating retinal autoantibodies lead to inflammation and downstream photoreceptor destruction [3]. Photoreceptor loss can also occur secondary to damage or dysfunction of adjacent cells and extracellular structures; for example, diseases a ffecting the retinal pigment epithelium (RPE), Bruch's membrane, or choroid can lead to increased oxidative stress and decreased metabolic support to the outer retina [4].

One approach for studying retinal degeneration is to characterize transcriptomic changes within diseased retina using microarrays or, more recently, next-generation sequencing of cDNA libraries (RNA sequencing, or RNA-Seq). Conventional gene expression studies with RNA-Seq have analyzed pools of retinal RNA from numerous cell types [5,6]. However, the high degree of cellular complexity and diversity in the human retina can prevent detection of even large gene expression changes that are

restricted to specific classes of cells that are relatively unrepresented in the pool [7]. This concern has been largely obviated by the development of single-cell RNA sequencing, which has recently been employed to characterize the transcriptome of individual retinal cell populations. The neural retina is well suited for dissociation into single-cells, and protocols for recovery of viable, singlet cells are well established [8,9]. Such protocols facilitated the exploration of the murine retina transcriptome in the first report of Drop-Seq single-cell RNA sequencing [10]. Since this initial investigation, several additional studies have described the transcriptome of murine retina [10–12] and more recently, human retina [13–15] at the single-cell level.

In this report, we describe the clinical course of a 70-year-old patient with progressive photoreceptor degeneration attributed to AIR. We perform single-cell RNA sequencing on paired foveal and peripheral retinal samples from this patient and four una ffected control patients to investigate how di fferent populations of retinal cells respond to photoreceptor degeneration. A total of 23,429 cells were recovered in this experiment, including 7189 cells from the AIR patient. This study provides insight into the responses of the retina to a blinding inflammatory condition at the cellular and transcriptional levels.
