Retina, retinol, retinal and the natural history of vitamin A as a light sensor

Abstract

Light is both the ultimate energy source for most organisms and a rich information source. Vitamin A-based chromophore was initially used in harvesting light energy, but has become the most widely used light sensor throughout evolution from unicellular to multicellular organisms. Vitamin A-based photoreceptor proteins are called opsins and have been used for billions of years for sensing light for vision or the equivalent of vision. All vitamin A-based light sensors for vision in the animal kingdom are G-protein coupled receptors, while those in unicellular organisms are light-gated channels. This first major switch in evolution was followed by two other major changes: the switch from bistable to monostable pigments for vision and the expansion of vitamin A's biological functions. Vitamin A's new functions such as regulating cell growth and differentiation from embryogenesis to adult are associated with increased toxicity with its random diffusion. In contrast to bistable pigments which can be regenerated by light, monostable pigments depend on complex enzymatic cycles for regeneration after every photoisomerization event. Here we discuss vitamin A functions and transport in the context of the natural history of vitamin A-based light sensors and propose that the expanding functions of vitamin A and the choice of monostable pigments are the likely evolutionary driving forces for precise, efficient, and sustained vitamin A transport.

Figure 1

Examples of structural divergence of biologically active retinoids. For simplicity, only representative biologically active endogenous retinoids are shown.

Figure 2

Schematic diagram of the localization of various opsins in human and mouse retina and retinal pigment epithelium (RPE). Only cells or cellular structures that express opsins are shown and are color-coded. There are species variations. Human, but not mouse, has the long-wave cone pigment. Neuropsin is expressed in the mouse retina, but not in the human retina.

Figure 3

Summary diagram of the key events in the evolution of vitamin A functions that coincide with the emergence of RBP/STRA6-mediated specific vitamin A transport.

Figure 4

Comparison of two retinal-based light sensing structures: the eyespot in Chlamydomonas reinhardtii and the human eye. The human eye depends on vitamin A not only for light sensing for vision and the biological clock, but also for embryonic development and for the maintenance of the cornea. Cells or structures that depend on vitamin A are labeled in red.