Treatment with Carbonic Anhydrase Inhibitors Depresses Electroretinogram Responsiveness in Mice

Sauvé, Yves; Karan, Goutam; Yang, Zhenglin; Li, Chunmei; Hu, Jianbin; Zhang, Kang

doi:10.1007/0-387-32442-9_61

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…DNP is protonophore that stimulates mitochondrial respiration at these non-toxic doses 30 , 41 , and OCT images were captured 1 h after injection. ACZ was dissolved in pH 9 phosphate buffer saline (PBS) to a final concentration of 25 mg/ml, and given to mice by i. p. injection at a dose of 250 mg/kg, and imaged 3 h after injection 56 . ACZ acidifies the subretinal space and suppresses the light–dark ELM-RPE difference as measured by diffusion MRI 22 , 57 , 58 .…”

Section: Methodsmentioning

confidence: 99%

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images

Gao

Bissig

et al. 2021

Sci Rep

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Human and animal retinal optical coherence tomography (OCT) images show a hyporeflective band (HB) between the photoreceptor tip and retinal pigment epithelium layers whose mechanisms are unclear. In mice, HB magnitude and the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. Here, we test the hypothesis that these two OCT biomarkers are linked to metabolic activity of the retina. Acetazolamide, which acidifies the subretinal space, had no significant impact on HB magnitude but produced ELM-RPE thinning. Mitochondrial stimulation with 2,4-dinitrophenol reduced both HB magnitude and ELM-RPE thickness in parallel, and also reduced F-actin expression in the same retinal region, but without altering ERG responses. For mice strains with relatively lower (C57BL/6J) or higher (129S6/ev) rod mitochondrial efficacy, light-induced changes in HB magnitude and ELM-RPE thickness were correlated. Humans, analyzed from published data captured with a different protocol, showed a similar light–dark change pattern in HB magnitude as in the mice. Our results indicate that mitochondrial respiration underlies changes in HB magnitude upstream of the pH-sensitive ELM-RPE thickness response. These two distinct OCT biomarkers could be useful indices for non-invasively evaluating photoreceptor mitochondrial metabolic activity.

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Section: Methodsmentioning

confidence: 99%

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images

Gao

Bissig

et al. 2021

Sci Rep

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“…The smaller increase in bicarbonate induced circulating current with acetazolamide in IS-in recordings meant that cones produced bicarbonate internally from CO 2 in equilibrium with bicarbonate in aqueous solution. These results help to account for the reduced photopic a-wave of the mammalian ERG particularly with bright flashes on administration of carbonic anhydrase inhibitor (Broeders et al, 1988; Odom et al, 1994; Sauvé et al, 2006) and indicate that it was not just due to acidosis. Dorzolamide inhibited recombinant murine carbonic anhydrase II in COS cells (Fig.…”

Section: Discussionmentioning

confidence: 80%

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Makino

Duda

Pertzev

et al. 2019

eNeuro

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The membrane guanylate cyclase, ROS-GC, that synthesizes cyclic GMP for use as a second messenger for visual transduction in retinal rods and cones, is stimulated by bicarbonate. Bicarbonate acts directly on ROS-GC1, because it enhanced the enzymatic activity of a purified, recombinant fragment of bovine ROS-GC1 consisting solely of the core catalytic domain. Moreover, recombinant ROS-GC1 proved to be a true sensor of bicarbonate, rather than a sensor for CO2. Access to bicarbonate differed in rods and cones of larval salamander, Ambystoma tigrinum, of unknown sex. In rods, bicarbonate entered at the synapse and diffused to the outer segment, where it was removed by Cl--dependent exchange. In contrast, cones generated bicarbonate internally from endogenous CO2 or from exogenous CO2 that was present in extracellular solutions of bicarbonate. Bicarbonate production from both sources of CO2 was blocked by the carbonic anhydrase inhibitor, acetazolamide. Carbonic anhydrase II expression was verified immunohistochemically in cones but not in rods. In addition, cones acquired bicarbonate at their outer segments as well as at their inner segments. The multiple pathways for access in cones may support greater uptake of bicarbonate than in rods and buffer changes in its intracellular concentration.

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“…It was reported that in the intact eye, in the transition from light to dark, oxygen consumption in the retina increases with a concomitant release of CO 2 into the subretinal space . Electroretinogram responsiveness in mice was depressed by CA inhibitors . A sporadic form of inherited Retinitis Pigmentosa (RP) is due to carbonic anhydrase IV gene mutations .…”

Section: Resultsmentioning

confidence: 99%

“…46 Electroretinogram responsiveness in mice was depressed by CA inhibitors. 47 A sporadic form of inherited Retinitis Pigmentosa (RP) is due to carbonic anhydrase IV gene mutations. 48 RP is a retinal dystrophy primary caused by the loss of rods in the peripheral retina.…”

Section: Atp Synthesis By Rod Discsmentioning

confidence: 99%

Functional expression of oxidative phosphorylation proteins in the rod outer segment disc

Panfoli

Calzia

Bruschi³

et al. 2013

Cell Biochemistry & Function

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The rod Outer Segment (OS) disc, an organelle devoid of mitochondria, is specialized in phototransduction, a process requiring a continual chemical energy supply. We have shown that OS discs express functional mitochondrial electron transport chains, Fo F1 -ATP synthase and the tricarboxylic acid cycle enzymes, all mitochondrial features. Here, we focus on oxygen consumption and adenosine triphosphate (ATP) synthesis by OS discs analysing electron transport chain I-III-IV and II-II-IV pathways, supported by reduced nicotinamide adenine dinucleotide and succinate, respectively. Interestingly, respiratory capacity of discs was measurable also in the presence of 3-hydroxy-butyrrate, a typical metabolic substrate for the brain. Data were supported by a two-dimensional electrophoresis analyses conducted as our previous one, but focused to those mitochondrial proteins that are involved in oxidative phosphorylation. Carbonic anhydrase was also found active in OS discs. Moreover, colocalization of Rhodopsin with respiratory complex I and ATP synthase seems a further step in the characterization of some proteins typical of the mitochondrial inner membranes that are expressed in the rod discs. The existence of oxygen utilization in the outer retina, likely supplying ATP for phototransduction, may shed light on some retinal pathologies related to oxidative stress of the outer retina.

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Treatment with Carbonic Anhydrase Inhibitors Depresses Electroretinogram Responsiveness in Mice

Cited by 8 publications

References 15 publications

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Functional expression of oxidative phosphorylation proteins in the rod outer segment disc

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