Systemic hypoxia dehydrates the space surrounding photoreceptors in the cat retina

Purpose. To assess the effects of systemic hypoxia and hyperoxia on the volume of the subretinal space (SRS). Methods. The authors measured the concentration of the extracellular space marker tetramethylammonium (TMA(+)) in the intact cat eye using double-barreled ion-selective microelectrodes. The retina was loaded with TMA(+) by a single intravitreal injection. Systemic hypoxia was induced by adding nitrogen to the breathing mixture, and hyperoxia was induced by adding oxygen. Results. Hypoxia produced a slow increase in dark-adapted [TMA(+)](o), which was prominent in amplitude in the distal portion of the retina, suggesting a shrinkage of the SRS, This effect was essentially proportional to the decrease in arterial oxygen tension (PaO2) below the normoxic level. Dark-adapted [TMA(+)](o) began to increase at a PaO2 of 60 to 80 mm Hg and was enhanced by 13% to 15% at a PaO2 of 40 mm Hg. Because of its slow onset, the size of the increase also was related to the duration of hypoxia. The light-evoked decrease in [TMA(+)](o) in the SRS was larger in amplitude during hypoxia than in normoxia. This difference increased with severity of hypoxia, beginning at approximately the same PaO2 as the increase in dark-adapted [TMA(+)](o). Interestingly, the hypoxic increase in amplitude depended on light intensity, i.e., it was proportionally greater at lower intensities versus higher ones. Background illumination suppressed the hypoxia-induced increase in [TMA(+)](o) in SRS, inhibiting it by approximately 50% at levels of hypoxia down to a PaO2 of 40 mm Hg. Systemic hyperoxia produced the reverse effect of hypoxia. Between two extreme states, e.g., illumination during hyperoxia (PaO2 > 200 mm Hg) versus severe hypoxia in darkness (PaO2 approximately 40 mm Hg), extracellular volume may change more than 4-fold. Conclusions. The observations of this study indicate that the space surrounding photoreceptors shrinks in response to hypoxia. This shrinkage should affect concentrations of all ions and metabolites located in the subretinal space.