OXYGEN-CONSUMPTION IN THE RAT OUTER AND INNER RETINA - LIGHT-INDUCED 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 twofold gr eater 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 (O-IR) was measured during dark and rod-saturating light adapt ation. The effects of function-specific chemical agents on Q(WR), Q(OR ) and Q(IR) during dark and light adaptation were determined. In addit ion, the oxidation-reduction (redox) potential of cytochrome a(3) of w hole, outer and inner retina was measured during dark and light adapta tion. During dark adaptation, the mean Q(WR) was 1.62 mu mol O-2 (mg d ry wt)(-1) hr(-1) and whole retinal level of reduced cytochrome a(3) w as 19%. They decreased by 24% and 37% during light adaptation, respect ively. To determine Q(OR) and Q(IR) during dark and light adaptation, the outer retina was pharmaeologically-isolated from inner retina usin g L-2-amino-4-phosphonobutyric acid plus kynurenic acid (APB/Kyn). Exp eriments 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 l ight 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 O-WR during light adaptation, respectively, (iii) the level of red uced retinal cytochrome a(3) in the outer, but not inner, retina was d ecreased 34% during light adaptation, (iv) during light adaptation, th e rate of QO(2) was equal in the outer and inner retina, and (v) the e ffects of APB/Kyn were reversible. These results establish that the me an rate of Q(IR) and retinal cytochrome a, are unchanged during dark o r 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, ou abain, Co2+ plus Mg2+ and verapamil-significantly decreased Q(WR) duri ng dark and light adaptation. A more detailed analysis revealed that I BMX and lead each selectively reduced (greater than or equal to 90%) Q (OR) during dark adaptation whereas Co2+ plus Mg2+ and verapamil each selectively reduced (greater than or equal to 93%) Q(IR) during dark a nd light adaptation. These results are consistent with the known pharm acological sites and mechanisms of these agents. Additional experiment s determined that the IBMX- and lead-induced inhibition of Q(OR) durin g dark adaptation resulted, either wholly or partially, from the influ x of extracellular Ca2+. During dark adaptation in Ca2+-free medium: ( i) Q(WR) and Q(OR) increased while Q(I)R was unchanged, (ii) Q(OR) was not decreased in the presence of IBMX and (iii) Q(OR) was only partia lly decreased in the presence of lead. These results are consistent wi th our recent findings that both Ca2+ and Pb2+ produce rapid, concentr ation-dependent decreases in retinal mitochondrial QO(2). Overall, the se results have relevance to normal retinal function, and possible sit es and mechanisms of retinal degeneration. (C) 1995 Academic Press Lim ited.