RESEARCH ADVANCE A novel acidification mechanism for greatly enhanced oxygen supply to the fish retina Christian Damsgaard1†*, Henrik Lauridsen2, Till S Harter3, Garfield T Kwan3, Jesper S Thomsen4, Anette MD Funder5, Claudiu T Supuran6, Martin Tresguerres3, Philip GD Matthews1, Colin J Brauner1 1Department of Zoology, University of British Columbia, Vancouver, Canada; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Scripps Institution of Oceanography, UC San Diego, La Jolla, United States; 4Department of Biomedicine, Aarhus University, Aarhus, Denmark; 5Department of Forensic Medicine, Aarhus University, Aarhus, Denmark; 6Universita` degli Studi di Firenze, Neurofarba Department, Sezione di Scienze Farmaceutiche, Florence, Italy Abstract Previously, we showed that the evolution of high acuity vision in fishes was directly associated with their unique pH-sensitive hemoglobins that allow O2 to be delivered to the retina at PO2s more than ten-fold that of arterial blood (Damsgaard et al., 2019). Here, we show strong evidence that vacuolar-type H+-ATPase and plasma-accessible carbonic anhydrase in the vascular structure supplying the retina act together to acidify the red blood cell leading to O2 secretion. In vivo data indicate that this pathway primarily affects the oxygenation of the inner retina involved in signal processing and transduction, and that the evolution of this pathway was tightly associated *For correspondence: with the morphological expansion of the inner retina. We conclude that this mechanism for retinal
[email protected] oxygenation played a vital role in the adaptive evolution of vision in teleost fishes. Present address: †Aarhus Institute of Advanced Studies & Section for Zoophysiology, Department of Biology, Aarhus Introduction University, Aarhus, Denmark The retina of vertebrates, containing the light-sensitive photoreceptors required for visual percep- tion, has a very high metabolic rate that must be supported by an adequate supply of O2 Competing interests: The (Linsenmeier and Braun, 1992).