PHOTOBIOLOGY OF THE RETINA.docx

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