Oxygen consumption in the rat outer and inner retina: light- and pharmacologically-induced inhibition.

Biochemical, physiological and histological data have established that 55–65% of retinal mitochondria are located in the photoreceptor inner segments and suggested that photoreceptors have at least a two-fold greater oxygen consumption (QO 2 ) than the remaining inner retina. QO 2 in isolated whole rat retina (Q WR ), outer retina (Q OR ) and inner retina (Q IR ) was measured during dark and rod-saturating light adaptation. The effects of function-specific chemical agents on Q WR , Q OR and Q IR during dark and light adaptation were determined. In addition, the oxidation-reduction (redox) potential of cytochrome a 3 of whole, outer and inner retina was measured during dark and light adaptation. During dark adaptation, the mean Q WR was 1·62 μ mol O 2 (mg dry wt) −1 hr −1 and whole retinal level of reduced cytochrome a 3 was 19%. They decreased by 24% and 37% during light adaptation, respectively. To determine Q OR and Q IR during dark and light adaptation, the outer retina was pharmacologically-isolated from inner retina using l -2-amino-4-phosphonobutyric acid plus kynurenic acid (APB/Kyn). Experiments in the presence or absence of APB/Kyn revealed that: (i) Q OR , but not Q IR , of the dark-adapted retina was decreased 37% during light adaptation, (ii) the outer and inner retina consumed 65% and 35% of the Q WR during dark adaptation, respectively, and 54% and 46% of the Q WR during light adaptation, respectively, (iii) the level of reduced retinal cytochrome a 3 in the outer, but not inner, retina was decreased 34% during light adaptation, (iv) during light adaptation, the rate of QO 2 was equal in the outer and inner retina, and (v) the effects of APB/Kyn were reversible. These results establish that the mean rate of Q IR and retinal cytochrome a 3 are unchanged during dark or light adaptation. In addition, they suggest that Q OR :Q IR in the rat may be modeled using a 65%:35% model during DA and a 55%:45% model during LA. All the function-specific agents—IBMX, lead, diltiazem, ouabain, Co 2+ plus Mg 2+ and verapamil—significantly decreased Q WR during dark and light adaptation. A more detailed analysis revealed that IBMX and lead each selectively reduced (⩾ 90%) Q OR during dark adaptation whereas Co 2+ plus Mg 2+ and verapamil each selectively reduced (⩾ 93%) Q IR during dark and light adaptation. These results are consistent with the known pharmacological sites and mechanisms of these agents. Additional experiments determined that the IBMX- and lead-induced inhibition of Q OR during dark adaptation resulted, either wholly or partially, from the influx of extracellular Ca 2+ . During dark adaptation in Ca 2+ -free medium: (i) Q WR and Q OR increased while Q IR was unchanged, (ii) Q OR was not decreased in the presence of IBMX and (iii) Q OR was only partially decreased in the presence of lead. These results are consistent with our recent findings that both Ca 2+ and Pb 2+ produce rapid, concentration-dependent decreases in retinal mitochondrial QO 2 . Overall, these results have relevance to normal retinal function, and possible sites and mechanisms of retinal degeneration.