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A new collaboration including scientists at Scripps Institution of Oceanography at the University of California San Diego shows a new mechanism in fish eyes that boosts the retina´s oxygen supply more than 10-fold and enhances the eye's ability to process visual input.  This mechanism for improved vision may have contributed to the extraordinary diversity and evolution of fishes, which today represent half of all vertebrates in the world. The study, published today in the journal eLife, included scientists from the University of British Columbia in Canada, Aahurus University in Denmark, and the University of Florence in Italy.  The National Science Foundation and UC San Diego Arthur M. and Kate E. Tode Research Endowment in Marine Biological Processes supported the research.          Visual input enters our eyes as light waves that are transformed by the eye's light-absorbing retina into electrical signals that are sent to the brain for interpretation. This energy-demanding process requires a lot of oxygen, which is supplied by a dense network of capillary blood vessels in most animal tissues. The fish retina does not possess an internal capillary network, likely to reduce light absorption by blood before the photons reach the photoreceptors. While this is expected to benefit the visual acuity of fish, excluding capillaries from the eye will also increase the distance that oxygen has to travel to the retina. The recent study investigated how fish manage to bridge this gap and oxygen can reach the retina. More than 300 million years ago, before the emergence of the first dinosaurs, hemoglobin in fish mutated to become much more sensitive to acid. Here, acidification of the blood releases a large part of hemoglobin oxygen into the surrounding tissues. This includes the oxygen release into the swim bladder, so fishes can remain buoyant at great depths under extreme pressure. However, the same mechanism for oxygen delivery may also allow fishes to deliver oxygen to their capillary-poor eyes. “It has been known for half a century that the fish eye can generate high oxygen pressures within the eye to drive oxygen diffusion into their large eyes,” said Christian Damsgaard, an assistant professor of animal physiology at Aarhus Institute of Advanced Studies and Department of Biology at Aarhus University, who is the lead author of the new study. “However, the physiological mechanism that can generate these high oxygen pressures in the fish eye has remained highly elusive. This is what we have now identified.” To identify the primary biochemical pathway involved in this superior mode of oxygen delivery in the fish eye, an international and interdisciplinary group of animal physiologists, molecular biologists, and pharmacologists joined forces.  “Here at Scripps we have excellent microscopy facilities, which allowed us to look at single cells within the blood vessels in the fish eye,” said Till Harter, a postdoctoral researcher at Scripps Oceanography who helped produce the images published in the study. “As expected, these cells had all the proteins that are required for acidifying the blood and enhancing oxygen delivery to the eye.” The research group identified a set of enzymes that first pumps acidifying protons into the blood vessels that reach the eye. Then, the enzymes transport the protons into the red blood cells, where they shed oxygen from hemoglobin into the retina. These findings suggest that the vascular beds within the fish eye act as an acidifying gas-gland similar to that found in their swim bladder. “A previous study from our lab identified similar proteins within the capillary bed of the fish’s inner ear”, said Garfield Kwan, a postdoctoral researcher at Scripps and NOAA Southwest Fisheries Science Center, and a co-author of the study. “We are currently investigating whether a similar oxygen delivery mechanism helps the inner ear maintain proper balance and hearing.” To investigate how this newly discovered oxygen supply mechanism affects vision, the group measured the function of the retina while blocking the mechanism using pharmacological compounds. Blocking the acidification mechanism in the fish eye rapidly impaired the function of the specific areas within the retina involved in signal-processing. Next, the group compared the anatomy of the retina in over 30 fish species and showed that species with the unique acidifying vasculature had markedly enlarged those specific signal-processing areas within the retina. “These interesting findings strongly suggested that the evolutionary origin of this superior mode of oxygen delivery to the eye allows fishes to better identify and track prey,” Damsgaard said. “This may have led to active feeding strategies in early fish evolution and fueled the adaptive radiation of fishes, which represent over half of all vertebrates.”  The same proton secreting protein involved in oxygen delivery in the fish eye is also essential for many other fascinating mechanisms in other marine organisms. They help sharks control blood pH, improve photosynthesis in algae within corals, and help bone-eating worms dissolve bones and giant clams burrow into reefs. It is also essential for the ability of diatom algae to make their external silica wall. “This proton pumping protein is found in all eukaryotic organisms,” said Martin Tresguerres, an associate professor at Scripps and  co-author of the study who was involved in the previous research about this proton pump.  “This is one of the most fascinating examples of a multifunctional enzyme, with its ultimate function depending on its association with other proteins and its specific localization within a cell,” he said. “Although this proton pump has been studied for almost 60 years, recent advances in microscopy and molecular techniques are allowing us to unveil novel aspects about its functions in diverse organisms.” -Adapted from Arhaus University