Active Blood Acidification Greatly Enhances Oxygen Supply to the Teleost Retina

Abstract

Most ray-finned fishes possess a unique system for retinal oxygen delivery, where intracellular acidification of red blood cells (RBCs) in the retinal capillaries induces oxygen offloading from pH-sensitive hemoglobin. A countercurrent vascular network, the choroid rete mirabile, posterior to the retina augments this “oxygen-secretory” mechanism and confers retinal PO2 values that can exceed 1300 mmHg in some species. We hypothesized that the choroid rete mirabile exerts an active role in intracellular RBC acidification to facilitate retinal oxygen secretion. We show the presence and enzymatic activities of extracellular carbonic anhydrase (CA) and vacuolar-type H+-ATPase (VHA) in the lumen of the choroid rete mirabile. These data are consistent with a pathway, where VHA secretes H+ into the choroid rete mirabile lumen, which combines with HCO3– to form CO2 (catalyzed by extracellular CA) that rapidly diffuses into the RBC facilitating hemoglobin oxygen offloading. Next, we validated the model in vivo by injecting an extracellular CA inhibitor (C18) into the dorsal aorta of anesthetized rainbow trout with a PO2 electrode implanted into the retina. Here, the inhibition of extracellular CA resulted in a rapid reduction in retinal PO2 from 517 to 226 mmHg within minutes. These data strongly support the proposed model for RBC acidification in the choroid rete mirabile. Further, in vivo data show that this mechanism primarily augments oxygen diffusion to the inner retinal segments involved in signal-processing and that the evolution of this pathway was tightly associated with the morphological expansion of this part of the retina. Together, these data suggest that the evolutionary origin of retinal oxygen secretion in the early history of the ray-finned fishes was associated with a greatly enhanced capacity for visual processing, potentially permitting improved visual prey detection and the colonization of novel environments.