The pigmented epithelium, a bright partner against photoreceptor degeneration

Sight depends on the intimate association between photoreceptors and pigment epithelial cells. The evolutionary origin of this cellular tandem can be traced back to the emergence of bilateral animals, at least 450 million years ago, as they define the minimal unit of the ancestral prototypic eye. Phototransduction is a demanding process from the energetic and homeostatic points of view, and not surprisingly photoreceptive cells are particularly susceptible to damage and degeneration. Here, we will examine the different ancillary roles that the pigmented cells play in the physiology and homeostasis of photoreceptors, linking each one of these processes to the most common hereditary retinal diseases. We will discuss the challenges and opportunities of recent therapeutic advances based on cell and gene replacement. The transition from animal models to clinical trials will be addressed for each one of the different therapeutic strategies with a special focus on those depending on retinal-pigmented epithelial cells. Finally, we will discuss the potential impact of combining CRISPR technologies with gene and cell therapy approaches, which - in the frame of the personalized medicine revolution - may constitute a leap forward in the treatment of retinal dystrophies.