grant

Regulators of retinal metabolism in healthy and degenerating retinas

Organization UNIVERSITY OF PITTSBURGH AT PITTSBURGHLocation PITTSBURGH, UNITED STATESPosted 1 Sept 2020Deadline 30 Jun 2026
NIHUS FederalResearch GrantFY2024(hydroxymethylglutaryl-CoA reductase (NADPH)) kinase5'-AMP-activated protein kinase5'-Adenylic acidAMP-activated kinaseAMP-activated protein kinaseAMPK enzymeAdenosine MonophosphateAdenylic AcidAffectAgeAge related macular degenerationAge-Related MaculopathyAgingAssayBioassayBiogenesisBiological AssayBody TissuesCatalytic CoreCatalytic DomainCatalytic RegionCatalytic SiteCatalytic SubunitCell BodyCell NucleusCellsD-GlucoseDNA ContentDNA IndexDNA PloidyDataData AnalysesData AnalysisDefectDevelopmentDextroseDimethylbiguanidineDimethylguanylguanidineDiseaseDisorderDrugsDysfunctionFunctional disorderGene ExpressionGene TranscriptionGenesGenetic AlterationGenetic ChangeGenetic TranscriptionGenetic defectGlnGlucoseGlutamate MetabolismGlutamate Metabolism PathwayGlutamineGoalsHMG CoA reductase (NADPH) kinaseHMG CoA reductase kinaseHMG coenzyme A reductase (NADPH) kinaseHereditaryInheritedIntermediary MetabolismKO miceKinasesKnock-out MiceKnockout MiceL-GlutamineLabelLeannessLightLinkMeasuresMediatingMedicationMetabolicMetabolic PathwayMetabolic ProcessesMetabolismMetforminMiceMice MammalsMitochondriaMitochondrial DNAMurineMusMutationN,N-dimethyl-imidodicarbonimidic diamideNuclearNucleusNull MouseOrigin of LifePPAR gammaPPAR-gPPAR-γPPARgammaPPARγPathway interactionsPeroxisome Proliferative Activated Receptor GammaPeroxisome Proliferator-Activated Receptor gammaPeroxisome Proliferator-Activated Receptor γPersonsPharmaceutical PreparationsPhosphorylationPhosphotransferase GenePhosphotransferasesPhotoradiationPhotoreceptor CellPhotoreceptorsPhotosensitive CellPhysiopathologyPloidiesProtein PhosphorylationPublishingQ LevoglutamideQ. LevoglutamideRNA ExpressionRNA SeqRNA sequencingRNAseqReceptor ProteinResearchRetinaRetinal DegenerationRetinal PhotoreceptorsRodRoleSortingTestingTherapeuticThiazolidinedione ReceptorThinnessTissuesTranscriptionTransphosphorylasesUnited StatesVisual Receptorage associatedage correlatedage dependentage dependent macular degenerationage induced macular degenerationage linkedage relatedage related macular diseaseage related macular dystrophyage specificageschromosome complementcofactordata interpretationdegenerative retina diseasesdesigndesigningdevelopmentaldrug/agentgain of functiongene functiongenome mutationhydroxymethylglutaryl-CoA-reductase kinasein vivoinherited retinal degenerationloss of functionmetabolism measurementmetabolomicsmetabonomicsmitochondrialmitochondrial dysfunctionmitochondrial metabolismmtDNAoxidative damageoxidative injurypathophysiologypathwayreceptorrepairrepairedresponseretina degenerationretinal degenerativeretinal degenerative diseasesretinal neuronscRNA-seqsenile macular diseasesingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial roletranscriptome sequencingtranscriptomic sequencinguptake
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Full Description

Abstract:
The retina has high metabolic activity, and retinal degenerations have been associated with mitochondrial

dysfunction, dysregulation of metabolism, and toxic oxidative damage. However, little is known about how

metabolism is maintained under normal conditions or is dysregulated in degenerating retinas. AMPK (AMP-

activated protein kinase) is a key regulator of metabolism in highly metabolic tissues and is a candidate to

regulate metabolism in photoreceptors, and its role in retinal metabolism will be rigorously studied in this

proposed project using both gain-of-function and loss-of-function approaches. Peroxisome proliferator-activated

receptor gamma coactivator-alpha (PGC-1α) and beta (PGC-1β) are key regulators of mitochondrial biogenesis.

Adenosine monophosphate dependent kinase (AMPK) is an important regulator of PGC-1 activity. Our goal in

this study is to determine the roles of AMPK and PGC-1 activity in retinal photoreceptors.

Grant Number: 5R01EY031720-05
NIH Institute/Center: NIH

Principal Investigator: John Ash

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