Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors Implications for Retinal Diseases 英文参考文献.docVIP

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Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors Implications for Retinal Diseases 英文参考文献.doc

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Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors Implications for Retinal Diseases 英文参考文献

DistinctSignatureofAlteredHomeostasisinAgingRod Photoreceptors:ImplicationsforRetinalDiseases SunilK.Parapuram1.¤a,RaduI.Cojocaru1,2.,JessicaR.Chang2,3.¤b,RituKhanna1,MatthewBrooks1,2, MohammadOthman1,SepidehZareparsi1¤c,NaheedW.Khan1,NorimotoGotoh2,TizianaCogliati2, AnandSwaroop1,2 * 1Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States of America, 2Neurobiology NeurodegenerationRepairLaboratory,NationalEyeInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica, 3HowardHughesMedical Institute-NationalInstitutesofHealthResearchScholarsProgram,Bethesda,Maryland,UnitedStatesofAmerica Abstract Background:Advancedagecontributestoclinicalmanifestationsofmanyretinopathiesandrepresentsamajorriskfactor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptorvulnerabilityandpotentialbiomarkersoftheagingprocessinthishighlyspecializedcelltypeareunknown. Methodology/Principal Findings: To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging(1.5,5,and12montholdmice).Weidentified375genesthatshoweddifferentialexpressioninrodsfrom5and12 montholdmouseretinacomparedtothatof1.5montholdretina.QuantitativeRT-PCRexperimentsvalidatedexpression changeforamajorityofthe25genesthatwereexamined.Macroanalysisofdifferentiallyexpressedgenesusinggeneclass testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age