Where vision begins

Abstract

The vertebrate retina appeared first some 500 million years ago in ancestral marine chordates, evolving since then in a multitude of unique specializations, adapted to the visuoecological lifestyles of each species. The first representation of a vertebrate retina section dates back to 1856 and is due to the German anatomist Heinrich Müller (Fig. 1a), who observed the slices of a fish retina that was fixed and hardened with chromic acid. The morphology of the main retinal cell types and how they are arranged in layers were drawn first in 1887 by the Italian scientist Ferruccio Tartuferi, a pupil of the Nobel prize laureate Camillo Golgi, by staining the retina (freshly dissected from humans, sheep, oxen, dogs, and rabbits) with the Golgi method (Fig. 1b). He was able to construct the first known basic wiring plan of the retina, from the dispositions and arrangements of the individual and clumped cells that had taken up the silver (although the process that select cells and stain them in their entirety is still unknown) [20]. The Tartuferi’s diagram identifies correctly the organization of the retinal layers and cells, an amazing accomplishment given the extremely limited knowledge about the retina at his times. Tartuferi agreed with the work of Müller [16] on the vascular shadow perception, with which he identified the “neuroepithelial layer,” hosting the rod and cones, the “first site” that is “excited by light” [20]. Obviously, no one at that time could even suspect what is now reported in every textbook, i.e., that vertebrate vision is initiated in the outer segments of the rod and cone photoreceptors. Following the absorption of a photon, the visual pigment rhodopsin (Rh, Fig. 2) undergoes several conformational changes to switch to its activated form, metarhodopsin II (Rh*), which is able to trigger a G-protein-coupled enzymatic cascade. The G-protein transducin (T) targets a specific phosphodiesterase (PDE6) that in turn hydrolyzes the second messenger cGMP leading to the closure of the cyclic nucleotide-gated channels (CNGC). The reduction of the cation influx through these channels, permeable to Na+ and Ca2+, causes membrane hyperpolarization and, in turn, a decrease or cessation of neurotransmitter release at the synaptic terminal, which is the message that is relayed to the second-order retinal neurons. This description is however grossly simplified, as shown by the immense number of studies, many of them reviewed in this special issue of the Pflügers Archiv: European Journal of Physiology on “Function and Dysfunction in Vertebrate Photoreceptor Cells.” These studies have shed light on the amazing performances of each one of these proteins, on the complex regulation exerted on them by a large number of other ones, and on the several types of ion channels shaping the photoresponse. The concerted action of all these proteins allows the visual system to perform effectively over twelve orders of magnitude of light levels with optimized spatial and temporal resolution. This huge range of light sensitivity is achieved by partitioning the task into the overlapping ranges operated by the slow, highly sensitive rod system (able to detect from the single up to 104 absorbed photons) and by the faster, less sensitive cone system (operating over about eight orders of magnitude of light sensitivities). Since the dynamic range of neuronal response in the visual pathway is limited to just three orders of magnitude or less, light adaptation must occur at the photoreceptor level in order to avoid that these neurons exceed their limited dynamic range and saturate. Several mechanisms aimed to reduce the photoreceptor sensitivity as the light intensity increases have been elucidated, but many others are still debated or yet concealed. As expected, several human vision disorders arise from heritable defect in one or more of the proteins * Giorgio Rispoli [email protected]