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 (QO2) than the remaining inner retina. QO2 in isolated whole rat retina (QWR), outer retina (QOR) and inner retina (QIR) was measured during dark and rod-saturating light adaptation. The effects of function-specific chemical agents on QWR, QOR and QIR during dark and light adaptation were determined. In addition, the oxidation-reduction (redox) potential of cytochrome a3 of whole, outer and inner retina was measured during dark and light adaptation. During dark adaptation, the mean QWR was 1.62 mumol O2 (mg dry wt)-1 hr-1 and whole retinal level of reduced cytochrome a3 was 19%. They decreased by 24% and 37% during light adaptation, respectively. To determine QOR and QIR 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) QOR, but not QIR, of the dark-adapted retina was decreased 37% during light adaptation, (ii) the outer and inner retina consumed 65% and 35% of the QWR during dark adaptation, respectively, and 54% and 46% of the QWR during light adaptation, respectively, (iii) the level of reduced retinal cytochrome a3 in the outer, but not inner, retina was decreased 34% during light adaptation, (iv) during light adaptation, the rate of QO2 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 QIR and retinal cytochrome a3 are unchanged during dark or light adaptation. In addition, they suggest that QOR:QIR 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, CO2+ plus Mg2+ and verapamil--significantly decreased QWR during dark and light adaptation. A more detailed analysis revealed that IBMX and lead each selectively reduced (> or = 90%) QOR during dark adaptation whereas CO2+ plus Mg2+ and verapamil each selectively reduced (> or = 93%) QIR 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 QOR during dark adaptation resulted, either wholly or partially, from the influx of extracellular Ca2+. During dark adaptation in Ca(2+)-free medium: (i) QWR and QOR increased while QIR was unchanged, (ii) QOR was not decreased in the presence of IBMX and (iii) QOR was only partially decreased in the presence of lead.(ABSTRACT TRUNCATED AT 400 WORDS)
Medrano
C J
CJ
College of Optometry, University of Houston, Texas 77204-6052, USA.
Fox
D A
DA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000221:Adaptation, Ocular / Q000502:physiology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D017936:Cytochrome a Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007736:Kynurenic Acid / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology; D008027:Light; D008274:Magnesium / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000378:metabolism*; D013053:Spectrophotometry; D014700:Verapamil / Q000494:pharmacology
D000613:Aminobutyrates; D017936:Cytochrome a Group; D007854:Lead; D003035:Cobalt; D014700:Verapamil; D007736:Kynurenic Acid; C012729:2-amino-4-phosphonobutyric acid; D008274:Magnesium; D015056:1-Methyl-3-isobutylxanthine