*2.1. Photoreceptor (PR) Cell Structure*

PR cells are sensory neurons within the retina that detect light and signal this event to other cells. Since PR cells are essential for vision, their loss can dramatically and negatively a ffect the quality of life. PR cells include rod and cone cells (Figure 1a,b) that occupy the outermost layers of the neurosensory retina. Although intrinsically photosensitive retinal ganglion cells have also been described as photoreceptors [22], we did not include them in this review, as their contribution to RD is unknown. Rod and cone photoreceptors possess unique structures that serve to compartmentalize processes that are critical for cell function and maintenance.


these structures represent a modified primary cilium that encompasses an extensive network of protein complexes that transport proteins and lipids and shares characteristics with primary cilia in many other cell types. The ciliary networks also function to prevent the flow of OS components to other parts of the cell and may associate with the intracellular trafficking apparatus to ensure the directed movement of needed components to the OS.

**Figure 1.** Retinal tissue organization emphasizing cell types and subcellular structures that may be sites of pathological processes in mouse models of photoreceptor (PR) cell loss. (**a**) A radial section of the posterior eye stained with hematoxylin and eosin shows the layered structure of the retina. CH, choroid; RPE, retinal pigment epithelium; IS, inner segment; OS, outer segment; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; NFL, nerve fiber layer. (**b**) Two PR cell types (rods and cones) and additional cell types that may be the target of processes implicated in PR cell loss. Dashed lines indicate alignment with retinal layers in (**a**). A columnar unit consisting of one cone and one Müller cell and roughly 20 rod cells is shown. (**<sup>c</sup>**–**f**) Details of PR and RPE cells. (**c**) PR cell OSs contain flattened discs (rod, left) or incomplete discs (cone, right) where the light sensing apparatus is located. OS tips engulfed by RPE cell apical processes are digested in phagolysosomes (Ph). (**d**) The base of the OS, the connecting cilium, and the apical portion of a rod cell IS (adapted with permission from [24]). The axoneme (Ax) and rootlet provide physical stability to the cilium. BB, basal bodies; CC-TZ, connecting cilium-transition zone; PCM, pericentriolar matrix; PCC/CP, periciliary complex/ciliary pocket; RER, rough endoplasmic reticulum. (**e**) The PR cell soma is largely occupied by the nucleus. (**f**) Rod and cone synaptic termini include presynaptic ribbons and associated neurotransmitter vesicles.


• The PR cell terminus contains ribbon synapses close to the presynaptic membrane loaded with vesicles containing the excitatory neurotransmitter glutamate (Figure 1f). In the dark, a steady-state level of glutamate is released at the synapse, which is reduced when the cells are hyperpolarized in the light. Changes in glutamate levels at the synapse signal postsynaptic secondary neurons in the inner nuclear layer, which communicate with ganglion cells on the vitreal surface of the retina that connect through long axons to the visual cortex of the brain.
