PHOTOBIOLOGY OF THE RETINA.docx
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PHOTOBIOLOGYOFTHERETINA
PHOTOBIOLOGYOFTHERETINA
Light-InducedDamagetotheRetina
MalgorzataRozanowskaa,BartoszRozanowskib,MichaelBoultonc
aCardiffVisionInstitute,SchoolofOptometryandVisionSciences,CardiffUniversity;MaindyRoad,CardiffCF244LU,UnitedKingdomrozanowskamb@cf.ac.uk
bDepartmentofCytologyandGenetics;InstituteofBiology,PedagogicalUniversity,Ul.Podbrzezie3,31-054Krakow,Poland
RozanoB@ap.krakow.pl
cDepartmentofAnatomyandCellBiology,UniversityofFlorida,1600SWArcherRoadPOBox100235,Gainesville,FL32610-0235,U.S.A.
MEBoulton@ufl.edu
Introduction
Photobiologyoftheretinacoversbroadaspectsofthephototransductioncascaderesponsibleforvisualperception,aswellasthepupillarylightreflex,andtheroleoftheretinainsettingupourcircadianrhythms.Allofthesefunctionsoftheretinadependontheabsorptionofphotons.However,excessiveexposuretolightresultsindamagetotheretina.ThephototransductioncascadeisdiscussedbyOysterinRetinaI:
PhotoreceptorsandFunctionalOrganization.Herewewillreviewcurrentunderstandingoflight-induceddamagetotheretina.Asthevisualcycleplaysanimportantroleinsusceptibilityoftheretinatolightdamage,certainaspectsofitwillbediscussedhereinmoredetail.
TypesofLight-InducedDamagetotheRetina
Throughoutlife,theeyeisexposedtodailyfluxesofsolarradiation.SolarradiationisfilteredbytheEarth'satmospheresothatatsealevelabout80%ofthesolarenergyisrestrictedtoanarrowspectralbandfromabout300nmintheultravioletto1100nmintheinfrared.Longerwavelengthsareprimarilyfilteredoutbyatmosphericwatervapour,whereasshorterwavelengthsareabsorbedbytheozonelayer.Furthermore,certainspectralcomponentsofsolarlightincidentonthecorneaarepartiallyfilteredoutbeforereachingthehumanretina
(1)(Figure1).Thecorneaabsorbswavelengthsbelow295nmwhilethelensintheadulthumaneyeabsorbsstronglylonger-wavelengthUVB(295-315nm),andthefullrangeofUVA(315-390nm).Boththecorneaandthelensalsoabsorbpartoftheinfraredradiation-mainlythewaterbandsat980nm,1200nm,and1430nm.Thevitreousabsorbslightabove1400nm,upto10
m.Thus,thenon-ionizingradiationreachingtheretinaistheso-called'visiblecomponent'oftheelectromagneticspectrum(390-760nm),andsomeofthenearinfrared(760-1400nm).
Figure1.Transmissionoflightthroughtheyoungadulthumaneyetotheretina[modifiedfrom(289)].
Inyoungchildren,someUV-BandUV-Acanreachtheretina,namelythespectralrangeof300-340nm,withamaximumofthattransmissionwindowofabout8%at320nm
(1).ThistransmissionbandisgraduallyreducedwhenmetabolitesoftryptophanabsorbingUVlightaccumulateinthelens.Bytheageof22years,only0.1%,andbytheageof60yearsvirtuallynoUVlightreachestheretinaexceptforaphakicindividuals.
Thetransmissionofvisiblelightdecreaseswithincreasingage,andariseslargelyfromage-relatedchangesinthecompositionofthelens,whichaccumulateschromophoresabsorbingshort-wavelengthvisiblelight.Lensesolderthan70yearsexhibitarelativelyslowincreaseintransmittancewithincreasingwavelength:
thetransmissionstartsatabout400nm,butdoesnotreachthemaximumuntilabout600nm.Overallthetransmissionofvisiblelightissignificantlyreducedinolderlenses,especiallyintheblueregionofthespectrum.Typicaldailyactivitiesarerelatedwithexposuresoftheretinatolightlevelswellbelowthethresholddosescausingacutephotodamagetotheretina(Figure2).However,directgazingatthesunorartificialsourcesofintensevisibleorinfraredlightcaneasilyleadtoexceedingthatthreshold,anddamagetheretina.
Figure2.Typicalretinalirradiancelevelsduringcommondailyactivities,retinalirradiancelevelsfromdifferentsourcesoflight:
thesun,frostedincandescentlamp,fluorescentlampandtypicalsizeoftheirimagesontheretinafora0.5sexposure.Thediagramalsoshowsthemaximalpermissibleexposure(MPE)for0.25sexposureoftheeyewitha2mmpupilandthedependenceofpupilsizeonretinalirradiance.Modifiedfrom(5,273).
Visibleandinfraredlightreachingtheretinacaninducetissuedamageviaatleastoneofthreefundamentalprocesses:
photomechanical(orphotoacoustic),photothermal(photocoagulation)andphotochemical,dependingonitsfluencerate,totaldoseandspectralcharacteristics.
Photochemicalinjury.Photochemicaldamageoccurswhenlightisabsorbedbyachromophoreandleadstotheformationofanelectronicallyexcitedstateofthatmolecule,whichthenundergoeseitherchemicaltransformationitselfand/orinteractswithothermoleculesleadingtochemicalchangesofbothinteractingmoleculesortoatransferoftheexcitationenergytotheothermolecules(Figure3).Importantly,whenphotochemicaldamageoccursthereisnosubstantialincreaseintemperatureofthetissue.Inaparticulartypeofphotochemicaldamage,photosensitizeddamage,thephotoexcitedchromophoreinitselectronicallyexcitedsingletstateundergoesintersystemcrossingandformsanexcitedtripletstate(Figure3).Theexcitedtripletstateisrelativelylong-lived,allowingforinteractionwithothermoleculesproducingfreeradicals-viaelectron(hydrogen)transfer(typeIofphotosensitizeddamage),orsingletoxygen,
-viatransferofexcitationenergyfromthephotosensitizerinthetripletstatetomolecularoxygen(typeIIofphotosensitizeddamage).Photosensitizerscanactascatalystsofextensivedamagewherenumerousfreeradicalsandsingletoxygenmoleculesaregeneratedbyasinglemoleculeofaphotosensitizer,whichisconstantlyrecycledtoitsgroundstate(Figure3B).
Figure3.Jablonskidiagramofphotoexcitationofamoleculeand3maindeactivationpathways(UpperFigure).Asmostbiologicallyrelevantmoleculesareinasingletstateintheirgroundstate(S0),theirphotoactivationleadstoanelectronicallyexcitedsingletstate(S1):
anelectronfromthehighestoccupiedmolecularorbital(HOMO)istransferredtothelowestunoccupiedmolecularorbital(LUMO).Fromthatelectronicallyexcitedsingletstatethereare3mainpathwaysofdeactivation:
1)thermaldeactivationisaradiation-lessprocess,calledalsointernalconversion(IC)wherethephotoexcitedmoleculereturnstothegroundstatereleasingtheexcitationenergyinaformofheatandnochangeinthemolecularspinoccurs;2)fluorescence(F)wherethephotoexcitedmoleculereturnstothegroundstatereleasingtheexcitationenergyinaformofanemittedphoton;3)intersystemcrossing(ISC)wherethephotoexcitedelectronchangesorientationofitsspinresultinginachangeinthemultiplicityandformationofanexcitedtripletstate(T1).Thelifetimeofanexcitedtripletstateisusuallyintherangeofmicrosecondsandlonger,thatisatleast3ordersofmagnitudelongerthanofanexcitedsingletstate(intherangeofps-ns).Anexcitedtripletstatedeactivatesviaradiation-lesstransitiontothegroundstateviaanintersystemcrossing(ISC)orareleaseofphotonknownasphosphorescence(Ph).
Longlifetimeofanexcitedtripletstateincreasestheprobabilityofinteractionwithothermolecules(LowerFigure).Photoexcitationofamolecule(P)toanexcitedsingletstate(1P)maybefollowedbyanintersystemcrossingandformationofanexcitedtripletstate(3P).Anexcitedtripletstate(3P)cantransferanelectron(orhydrogen)to/fromanothermoleculeleadingtoaformationofaradicalpair(TypeIofphotosensitizeddamage).Interactionofanexcitedtripletstatewithmolecularoxygen(whichisinatripletstateinitsgroundstate)mayleadtoanenergytransfer(typeIIofphotosensitizeddamage).Asaresult,thephotoexcitedmoleculereturnstoitsgroundstatewhileoxygenisactivatedtoanexcitedsingletstate,calledsingletoxygen(1O2).Chromophoreswhichuponphotoexcitationundergointersystemcrossingandproducefreeradicalsandsingletoxygenareknownasphotosensitizers(P).Asaresultofaninteractionofthetripletstatewithanelectrondonor(LH),suchasanunsaturatedlipid,theformedradicalanionofthephotosensitizermaydonatetheelectrontooxygenleadingtotheformationofsuperoxideradicalanion(O2.-).Thefreeradicalformedfromtheelectrondonorafterhydrogenabstraction(L.)cangiverisetoafreeradicalchainofperoxidationofbiomoleculessuchaslipidsandproteins.L.mayinteractwithoxygenformingaperoxylradical(LOO.).Theperoxylradicalmayabstractanelectron/hydrogenfromothermoleculesresultinginaformationofanotherL.andahydroperoxide(LOOH).Hydroperoxidesmaybecomedecomposedbyredoxactivemetalions,suchasiron,leadingtotheformationofmorefreeradicals.Asinglemoleculeofaphotosensitizermayproducenumerousfreeradicalsandsingletoxygenmoleculesaslongasitisrecycledtothegroundstateandphotoexcitedbysubsequentphotons.
Photosensitizeddamagemediatedbyoxygen(photodynamicdamage)hasbeenemployedinphotodynamictherapy(PDT)todestroytumoursandunwantedretinalneovascularisation.InPDTaphotosensitizingdrugisdeliveredtothetissueofinterestfollowedbyirradiationwithanappropriatelaserlighttotriggerthephotodynamicdamage.However,theretinacontainsanumberofendogenousphotosensitizerswhichcanbeexcitedbyvisible/infraredlightreachingtheretina.Theouterretina[photoreceptorsandretinalpigmentepithelium(RPE)],isimmediatelyadjacenttothechoroidalbloodsupplyandthushighlyoxygenated.Therefore,thesearepotentiallyfavourablecondit