Vision is our gateway to perceive the world around us. This is made possible by specialized cells in the eye that convert light into a biological signal that can be interpreted by the brain. These cells are called photoreceptors and come in two shapes. Rod photoreceptors are exquisitely light sensitive but cannot convey color information, while cone photoreceptor function under brighter light conditions and can convey not only brightness but also color information. There is only one rod type in vertebrates, while there are different cone types that are tuned to cover different colors of the light spectrum. Humans have three subtypes that are most sensitive to blue, green and red light, while zebrafish have an additional subtype sensitive to ultraviolet light.
Neuroscientists are fascinated by the huge range of light intensities that the visual system can cope with. Our eyes support vision at both a moonlit night and a bright summer day. The brightest light is about a 100 billionth times brighter than the dimmest light that we can perceive (think of a 1 followed by 11 zeros, or the range of weight from 1 gram and 10 million tons!). This remarkable task is in part achieved by having a dedicated low light system (using rod photoreceptors) and a bright light system (using cone photoreceptors) and in part by sophisticated biochemical regulatory mechanisms intrinsic to photoreceptors. The later system is especially important for cone photoreceptors, which have the largest range of light sensitivity and are also the one that we humans rely on for most of our daily lives (thanks to artificial lighting).
The intriguing biology of cone photoreceptors is difficult to study in humans for practical and ethical reasons, but also
nocturnal rodents such as mice are not well suited, due to their paucity of cone photoreceptors. Here the properties of the visual system of zebrafish come in handy, since cone photoreceptors are dominating zebrafish vision. The young larva even exclusively relies on cone photoreceptor function to support vision. Scientists have developed a range of behavioral and electrophysiological methods to precisely measure visual performance. Hence we are able to spot even subtle visual impairment already at larval stages. Reassuringly, electrophysiological recordings of the eye are directly comparable with measurements taken in mice and humans.
Within a cell, also within a cone photoreceptor cell, the genetic materials lies. The genetic material, DNA, includes the construction plan for each cell type. Some proteins/molecules are only produced by a special cell type. Proteins can act as messengers that influences other cells or processes within the cell and can also influence its function. Imagine a construction site: proteins are the workers, DNA is the project leader in the nucleus. Many of these proteins are also known to malfunction in inherited ocular diseases of humans. Other molecules from the outside can also influence cells. In all neurons, calcium is a messenger that triggers reactions. Sophisticated read-out measurements can now be applied to larvae where certain protein functions have been compromised by pharmacological or genetic means.
Studies have shown that adaptation of cone photoreceptors to light is dominated by a calcium dependent regulatory mechanisms. Calcium influences the activation of visual pigments within a photoreceptor. Artificial proteins can mimic and influence natural proteins that are specific to cone photoreceptors. Additionally, there is a larger variety of calcium binding proteins in cones. A deeper understanding of these mechanisms will not only address the long standing question of adaptation, but will also shine light on blinding diseases, such as retinal dystrophies and age-related macular degeneration.