pH in the vertebrate retina and its naturally occurring and pathological changes

This review summarizes the existing information on the concentration of H⁺ (pH) in vertebrate retinae and its changes due to various reasons. Special features of H⁺ homeostasis that make it different from other ions will be discussed, particularly metabolic production of H⁺ and buffering. The transretinal distribution of extracellular H⁺ concentration ([H⁺]_o) and its changes under illumination and other conditions will be described in detail, since [H⁺]_o is more intensively investigated than intracellular pH. In vertebrate retinae, the highest [H⁺]_o occurs in the inner part of the outer nuclear layer, and decreases toward the RPE, reaching the blood level on the apical side of the RPE. [H⁺]_o falls toward the vitreous as well, but less, so that the inner retina is acidic to the vitreous. Light leads to complex changes with both electrogenic and metabolic origins, culminating in alkalinization. There is a rhythm of [H⁺]_o with H⁺ being higher during circadian night. Extracellular pH can potentially be used as a signal in intercellular volume transmission, but evidence is against pH as a normal controller of fluid transport across the RPE or as a horizontal cell feedback signal. Pathological and experimentally created conditions (systemic metabolic acidosis, hypoxia and ischemia, vascular occlusion, excess glucose and diabetes, genetic disorders, and blockade of carbonic anhydrase) disturb H⁺ homeostasis, mostly producing retinal acidosis, with consequences for retinal blood flow, metabolism and function.