310RJRossorderof101improvestheacuitybyonelineontheSnellenchartThe - PDF document

*310R.J.Rossorderof10:1improvestheacuitybyonelineontheSnellenchart.Theeffectisratherlessforobserverswithgoodvisionthanforthosewithpoorvision,especiallyforhighlevelsofillumination.However,theresultisprobablyausefulworkingrule.Thereweresomedeviationsfromthegeneralrule-bysomesubjects,whicharenotshownbytheaveragedcurves,butthereisevidencethattheerrorswereprobablyexperimentalandnotsystematic.ThedatawouldsuggestthatitisnecessarytosetsomestandardofilluminationoftheSnellenchart,especiallywhenthisisusedasapasstestofvisualacuityforentrantstoatradeorprofession.Theinvestigationwasnot,ofcourse,concernedwiththeoptimumlevelofilluminationforclinicalpractice,althoughitwouldbeofinteresttoknowtherangeofilluminationlevelswithinwhichclinicianswouldnormallvwork.Asurveyofclinicalpracticewasmadein1928intheU.S.A.,*butnorecentsurveysappeartohavebeenmadeinthiscountry.Itisrealisedthatforvisualexaminationsconductedunderunfavourableconditionsof-work-ing,theclinicianoftenfindsitimpossibletoobtainthedesiredstandardoflighting.Theresultsofthisstudywill,however,indicatetohimtheallowancewhichshouldbemadeforsuchdeficienciesinillumination.TheinvestigationispartoftheresearchprogrammeoftheBuildingResearchBoardoftheDepartmentofScientificandIndustrialResearch,andthisnoteispublishedbypermissionoftheDirectorofBuildingResearch.Theauthorswouldliketoacknowledgethehelpoftheircolleagueswhoassistedintheexperimentalwork.THEFORMATIONOFTHEINTRA-OCULARFLUIDS.STUDIESOFTHEUREACOMPONENTOFTHEAQUEOUSHUMOURBYE.J.RossFromtheDepartmentofPhysiology,UniversityCollege,andtheOfhthalmologicalResearchUnitM.R.C.,InstituteofOphthalmology,LondontIThaslongbeenestablishedthattheconcentrationofureaintheaqueoushumourislessthanthatinthe

bloodplasma.Aftermakingallowanceforthe7percent.differenceinproteincontentbetweenaqueoushumourandplasma,theratiooftheureacon-centrationsofthesetwofluidshasbeendeterminedbyvariousworkersusingdifferentchemicalmethodsasfollows:*R.S.BURNAPandE.C.JACKSON(1928).Trans.I.E.S.(U.S.A.),23,1153. UREAINAQUEOUS.HUMOURSpecies7oxen......7dogs2horses.Horse(pooledaqueousand"typical"plasma)14cats10dogs,3rabbits1dog,..2cats4rabbits21cats3cats4rabbits14rabbits...MethodMeanratioUrease-hypobromiteUreaseUrease-gasometricAeration-titrationConductimetricAeration-NesslerisationUrease-NesslerisationAeration-titrationUrease-diffusion0.890.820.870.940.750.700.900.730.770.660.88ReferenceAndresen(1921)Duke-Elder(1927)Adler(1933)Walker(1933)Benham(1937)Moore,ScheieandAdler(1942)Scheie,Mooreand-Adler(1943)KinseyandGrant(1942)KinseyandRobison(1946)Iftheblood-aqueousbarrierwereasimplesemi-permeablemembraneandtheaqueoushumouradialysateorultrafiltrateofthebloodplasmarnon-lectrolytessuchasureawouldbeequallypartitionedperunitvolumeofwaterbetweentheplasmaandtheaqueoushumour.Theexistenceofaureadeficitintheintra-ocularfluidsindicatesthateitherthenatureoftheblood-aqueousbarrier-orconditionswithintheeyeare.suchastomodifythisequilibrium,by:-(a)selectivesecretionofureaacrossthebarrieroutoftheeye(Adler,1933).(b)utilisationofureawithinthe-eye,orby(c)theexistenceofacontinuousbulkoutflowofaqueoushumourfromtheeyesothattherateofdrainageofureafromtheeyeexceedstherateofentryofthissubstanceintotheeye(KinseyandGrant,1942.)Irithepresentpaperakineticstudyofthepermeabilityoftheblood-aqueousandblood-vitreousbarrierstoureahasbeenunder-taken,theaqueous/plasmaconcentrationratiohasbeenre-determined,themechanismofentryofureain

totheeyestudiedandevidenceofutilisationofthissubstanceinvestigated.Its31 modeofexitfromtheeyewill-beconsideredinasubsequentpaper.PartI-KinkticStudiesTHEPERMEABILITYTO-UREAOFTHEBLOOD-AQUEOUSBARRIERExperimentalInordertodemonstratethattheblood-aqueousbarrierispermeabletoureaakineticstudyofthetransportofthissubstancefromtheplasmatotheintra-ocularfluidswasunderta,ken.Theprincipleunderlyingthistypeofexperimentwastomaintainaconstanthighblood-ureabycontinuousintravenous-injectionofanisotonicsolutionintoananimalunderpentabarbitone(Nembutal)anaesthesia.Therenalvesselsweretiedtopreventrapidexcretionofthesubstanceduringtheinjection.Oneeyewasenucleatedimmediatelybeforetheinitialinjectiontogiveavaluefortheinitialureaconcentrationwithintheeye:asampleofbloodwassimultaneouslytakenfromthefemoralartery.Aninitialinjectionof20mls.of6percent.ureawasthenmadewithinoneminutetoraisethebloodurearapidlytoafigureofbetween100and200mg./I00ml.H20,andfurtherinjectionsweremadeatintervalstomaintainthishighbloodlevelsinceexperiencehadshownthatastablelevelcouldbemaintainedbysuitableboostsofureasolution.Samplesofbloodwereremovedat10minuteintervalstochecktheconstancyofthisbloodlevel.Afterasuitableinterval(30or60mins.)theothereyewasenucleatedandthefinalbloodsampletaken.Fluidswereremovedfromtheeyeasfollows:aqueouswaswithdrawnfromtheanteriorchamber,immediatelyafterenucleation,bymeansofaclean,drysyringe;thevitreousbodywasobtainedbyfreezingtheenucleatedeyeinsolidCO2,cuttingthefrozeneyeroundtheequator,removingthefrozenvitreouswithforceps,thawingitandforcingitthroughaglasswoolfiltertobreakupitsgelstructure.Ureainthisandallsubsequentexperimentswasdeterminedbytheurease-micro-diffusionmethodofConway(1946).This

'method-wasfoundtogiveconsistentandaccurateresultswithfluidsoflowandofhighproteincontent,fullrecoveryofaddedureawithin1percent.beingobtainedwithplasma,aqueousandvitreous.Thecorrectionforplasmaproteinswastakenas7percent.andallresultsarecalculatedasmg.per100mls.ofwater.Inallexperimentsitisassumedthattheureacontentoftheaqueousofapairofnormaleyesisidentical;determinationsoftheureacontentsoftheaqueousofthetwoeyesofapairshowthatthisassumpionisjustifiedwithin1percent.ResultsDetailedresultsarepresentedinTableI.Theseresultshavebeencalculatedintermsofthepermeabilityconstantsforaqueoushumour(KA)andforthevitreousbody(Iv)asdefinedbyDaVson,(S-Al)andQuilliam(1940),whereK=1001lg(S-A2)(t2-t1)(S=meanplasmaureaconcentration;A1=initialaqueousureaconcentrationattimet1;A2=finalaqueousureaconcentrationattimet2.Timeisexpressedinhours.)Theresultsshowthattherateofpenetrationofureaintotheaqueousisconsistentlyhigherthanthatintothevitreous:meanKA=119,meanKv,=5-4.,312.R.J.Ross UREAINAQUEOUSHUMOURTABLEIKINETICSTUDIES-RATEOFPENETRATIONOFUREAINTOTHEEYE(CAT)(a)Penetrationintotheaqueoushumour.ThepermeabilityconstantKA=100log(S-A1)1(Concentrationofureaexpressedasmg/100gH2O)Blood1Blood272.058.021.170.153.Z48.381.645.659.955.658.688.375.0124.394.268.2169.8.154.785.9149.5114.0214.5131.7171.6183.7135.4Aqueous152.045.615.857.0'35.054.268,935.136.343.546.390.464.7Time.Aqueous2(mins.)I_-I,_63.150.823.267.845.861.081.467.592.755.498.3127.195.5333230303030301221o333123120122KA13.29.414.28.78.220.814.613.28.111.211.311312.2Mean11.9-1.5(b)Penetrationintothevitreousbody.PermeabilityconstantKV=100log(S-V2)142-ti)(Concentrationofureaexpressedasmg/100gH20)Expt.Blood1BloOd2Vitreous1Vitreous2t21nS1|KVmins.2391.222

5.669.5113.01227.02759.9214.559.383.61233.62855.6131.724.929.3333.52958.6171.648.073.41234.93088.3180.769.594.61205.53175.0135.462.685.91228.2Mean5.440.6PartII-StaticStudies(a)IHEAQUEOUS/PLASMARATIOExperimentalFluidswereremovedsimultaneouslyfromanimalsunderpentabarbitoneanaesthesiabythemethodsalreadydescribed.313Expt.1012131516172123272829\3031 R.J.RossPLAMALMEACNGOENTRATIONOFUNANAESTHETI5EDRAI&BITSampestaktnathalF-hourintervals.IsII--atooO*oaol,0o15301100123013133014.0..1.eFIG'.1.Astudywasalsomadeofthefluctuationsofthebloodurealevelintheunanaesthetisedanimalbytakingbloodsamplesathalf-hourlyintervals.Theresults,whichareplottedinFig.1,showthatinthecourseof3hourstheureaconcentrationvaried-between59and78mg.percent.,adifferenceof24percent.whichwillaccountforthewidescatteroftheexperimentalratiossincechangesofureaconcentrationintheaqueouswilllagbehindthechangesintheblood.TABLEIITHEDISTRIBUTIONOFUREABETWEENBLOOD'PLASMA,AQUEOUSHUMOURANDVITREOUSBODYOFCATS(Concenitrationofureaexpressedasmg/100gH20)Plasma57.772.058.021.170.153.232.630.281.645.647.159.955.658.675.0AqueousVitreous45.752.045.615.857035.0224625.468.935.135.036.343.546.364.751.444.144.934734.248.062.6AqueousPlasma0.800.720.780.750.810.660.690.840.840.770760.610.780.790.86VitreousPlasma0.890.610.770.760.730.820.83Means0.76±0.0130.77±0.012314..I09Lgoar7C.3ZE:bi14)0wooExpt.9101213151618202123252728'2931 URRAINAQUEOUSHUMOURTHEDISTRIBUTIONOFUREABETWEENTHEBLOODPLASMA4NDAQUEOUSHUMOUROFRABBITSExpt.PlasmaAqueousAqueous/Plasma4540.431.00.764774.859.90.804848.732.80.685054.040.50.745165.852.20.795331.025.40.795448.534.00.705552.037.40.725771.950.30.745866.552.50.79Mean0.75+0.02ResultsThedistributionofureabetweenaqueoushum

our,vitreousbodyand'plasmaisshown'inTableII.Theexistenceofadeficitofureaintheintra-ocularfluidscomparedwit.htheplasmawaterisconfirmed.Themeanaqueous/plasmaratioof15catswasfoundtobe076;thatof10rabbits0-75;themeanvitreous/plasmaratioof7catswas0,77.Infinityvaluesobtainedbymaintainingthebloodconcentrationatahigh'levelformanyhoursshowedthatapparentequilibriumbetweenthetwofluidshadbeenre-establishedattheendof3.-hours:thisinfinityratiohadameanvalueof0173.(b)THEUTILISATIONOFUREAWITHINTHEEYEUreaisregardedastheend-productofnitrogencatabolisminthemammal,andnoevidencehassofarbeenadducedthatthissubstanceplaysanypartinthesyntheticprocessesofthebody.Thepossibilitythat'thedifferenceintheureaconcentrationofbloodandintra-ocularfluidsmaybeduetoutilisationwithinthe.eyebythemetabolicactivitiesofthelens,ciliarybodyorretinawasneverthelessexploredbybothinvitroandinvivoexperiments.INVITROEXPERIMENTSStudy'oftheexchangebetweenthelensanditsenvironmentwasmadewithlensesexcisedfromtheenucleatedeyesofrabbitsandcats.315 Assuming(1)thatureaenterstheeyebyaprocessofdiffusion,secretion,orfiltration,notyetfullyelucidated,andisremovedbvdrainage,(2)thattheureaconcentrationofthefluidcrossingtheblood-aqueousbarrierisidenticalwiththatofplasma,(3)thatthedrainageratefromtheanteriorchamberis4c.mm.permih.(KinseyandGrant,1942;preliminaryresultsofstudiesinthislaboratoryindicatethattherateismuchhigherinthecat),arid(4)thatthebloodureaconcentrationis40mg.percent.,thattheaqueous/plasmaratiois075,and(5)thatthevolumeofaqueoushumourinthecatis10ml.,thenthequantityofureaenteringtheeyeperhouris404X/40OOx1-x60mg.andthequantityleavingtheeyeperhouris/304ox,OOx60Jmg.11,000~6.gItfollowsthatthequantityofurearemovedperhourfrom

theaqueoushumourbetweenitsentranceto,anditsexitfrom,theeyewillbe(10x4x60)-mg.=0024mg.perhour.Ifthemetabolicactivityofthelensisthefactorresponsiblefortheremovalofureafromtheaqueoussoastoaccountforanaqueous/plasmaratioof075,thenthesurvivinglensimmersed-inaphysiologicalmediumcontainingureashouldremoveureafromthismediumataconstantrateof0-024mg.perhour.ExperimentalThelenswasremovedfromtheexcisedeye,driedonfilterpaperandweighed,thewholeprocedureoccupyinglessthan10minutes.Itwasthentransferredtoaspecimentubecontainingfreshoxaqueousfromeyesobtainedfromaslaughter-houseandkeptoniceuntilused;tothismediumatpH7-4ureawasaddedtogivetherequiredconcentration.Inthefirstsetofexperimentsthelenseswereincubatedfor24hoursat0°C.,insubsequentexperimentstheincubationtimewas2hoursat37'C.;thereisnoobviouscriterionofviabilityofalens,anditwasconsideredprobablethatthesurvivaltimeofanisolatedlenseveninaphysiologicalmediumisamatterofafewhoursonly.Theureaconcentrationofthisoxaqueousmediumwasfortifiedbyaddedureasothatsamplescontainingapproximately20,50and80mg.percent.wereobtained:the2ml.quantitiesemployedineachexperimentwouldthuscontain0-4,10and16mg.ofurearespectively.Afterincubationfortherequiredtimetheureaconcentrationofthemediumandofablankcontrolofthesamesolutionwasdetermined.R.J.Ross316 UREAINAQUEOUSHUMOURTABLEIIIEXPERIMENTSONSURVIVINGCATLENSESINCUBATEDFORASTATEDTIMEATASTATEDTEMPERATUREINOXAQUEOUSCONTAININGVARYINGUREACONCENTRATIONSTOSHOWTHEQUANTITYOFUREAEXTRACTED}FROMORAWIYEDTOTHEMEDIUMBYTHELENSDURINGINCUBATION(Ureaconcentrationsexpressedasmg/l00gH20)Ureaconc.ofaqueousUreaconc.ofUreaconc.ofofeyefromwhichmediumbeforemediumafterlenswasexcisedincubationincubation(i)Incubationfor24hrs.at0°C.57.049

.744.957.049.751.150.350.553.350.349.752.5(ii)Incubationfor2hrsat37°C.53.680.862.553.680.859.940.179.147.940.179.14q.650.049.150.850.049.153.440.149.151.440.149.156.525.115.618.725.115.619.320.318.625.120.318.624.0317ResultsDetailedresultsarepresentedinTableIII.Theyshowthatsuchdifferencesasexistintheureaconcentrationofthemediumbeforeandafterimmersionof-thelensinitfortwohourscanbeaccountedforbydiffusionofthesubstancefromamediumwithhigher,toamediumwithlowerconcentrationofurea;thusureaisremovedbythelensfromthemediumwhenthiscontainsahighconcentrationofthesubstance,butis-addedtothemediumwhentheureaconcentrationofthemediumisbelow.thatoftheaqueouswithwhichthelenswaspreviouslyin'equilibrium.INVIVOEXPERIMENTS(i)ONTHEEXCISEDEYEExperimentalThequestionoftheutilisationofureabythestructureswithintheeyewasfurtherinVestigatedbyremovingbotheyesfromtheanimal(rabbit)withinasshortaspaceoftimeaspossible,evacuatingtheaqueousfromoneofthepair 318R.J.'Rossinmediatelvanddeterminingtheureaconcentrationofthisfluid.Thefluidoftheothereyewasevacuatedafterithadbeenkeptat37'C.fortwohoursanditsureaconcentrationdetermined.Anydifferenceintheureaconcentrationoftheaqueousinthe-twoeyeswouldindicateutilisationofureawithintheeyebysuchvitalprocessesascontinuedtofunction.TABLEIVEXPERIMENTSON-fHEEXCISEDEYESHOWINGTHEUREACONCEN-TRATTONOFTHEAQUEOUSHUMOUROFAPAIROFEYES,ONEATTHETIMEOFEXCISIONANDTHEOTHERTWO'HOURSAFTEREXCISION.(RABBITS).(Ureaconcentrationexpressedasmg/100gH20)Ureaconc.ofaqueousintwoeyesofapair(i)at-timeof(ii)2hrs.afterexcisionexcision65.264.045.844.056.554.944.043.549.248.0ResultsResultsarepresentedinTableIV:theseshowthatthedifferencesinconcentrationinitiallyandattheendofthetwohoursaretoosmalltoa

ccountforautilisationsufficienttolow'ertheaqueousureaconcentrationto25percent.belowthatofblood.Thevolumeofarabbit'saqueousisabout025ml.sothatadifferenceof1-2mg.percent.representsalossofonly0-0015mg.perhour:thetheoreticalratetoachievethe25percent.deficitis0006mg.perhour.(ii)EXPERIMENTSONTHEAPHAKICANIMALExperimentalIfthelensisthefactorresponsibleforremovingureafromtheintra-ocularfluids,theaphakiceyewillshowanaqueous/plasmaratiowhichapproachesunity.Thelensofoneeyewasremovedinaseriesoffiverabbitsbythestandardsurgicalprocedureforextra-capsularextraction.Afteranintervalofsixweekstoallowforcompletehealing,fluidswerewithdrawnfrombotheyessimultaneouslyandabloodsampleobtainedfromtheaukralvein.Utilisationofureaby;thelenswouldresultinalowerconcentrationofureaintheunoperatedeyecomparedwiththe,aphakiceye.ResultsResultspresentedinTableVshowthattheunoperatedeyeconsistentlycontainedaslightlylowerureaconcentrationthandidtheaphakiceye.Themeanaqueous/plasmaratioofthe UREAINAQUEOUSHUMOURTABLEVEXPERIMENTSONTHEAPHAKICEYE.UREACONCENTRATIONOFAQUEOUSHUMOURINTHENORMALANDTHEAPHAKICEYEOFAPAIR.(RABBITS).(Concentrationofureaexpressedasmgf100gH20)PlasmaNormalAqueousAphakicAqueouseyePlasmaeyePlasma33.325.40.7627.70.8371.255.30.7757.10.8046.336.60.7937.90.8289.868.90.7671.20.8061.044.50.7347.50.78normaleyeis0-76,that-oftheaphakiceyeis081;althoughtheaqueous/plasmaratioisraisedintheaphakiceyeithasnotbecomesufficientlyclosetounityforutilisationofureabythelenstobetheexplanationoftheureadeficitwithintheeye.PartIII-Theroleofultrafiltrationintheformationoftheintra-ocularfluids(IncollaborationwithE.'Ba'rany*)KinseyandGrant(1942)concludefromtheirstudyofaqueoushumourdynamicsthatelectrolytesaresecretedacro

sstheblood-aqueousbarrierbutthatwaterandnon-electrolytesentertheeyebyultra-filtration.Forultra-filtrationtoseparateafluidfromthebloodagainstthecolloidosmoticpressureoftheblood(about25mm.Hg)andagainsttheintra-ocularpressure(25-30mm.Hg)acapillarypressuregreaterthan50-55mm.Hgwouldberequired;thegreaterthecapillarypressureabovethis-levelthegreaterwillbetherateofultra-filtration.Intheabsenceofanycompensatorymechanismstabilisingcapillarypressure(andobservationsbyBAranyofthlecapillariesofarabbit'searhaverevealednosuchmechanism)anyalterationofarterialpressurewillmateriallyaffectthedrivingforceacrossthemembraneand,therefore,therateofultra-filtration.Ameasureofthepartplayedbyultra-filtrationcanthusbeobtainedexperimentallybyvariationofthispressurefactor.Reductionofthelocalcapillarypressureandoftheintra-ocularpressurecanbeproducedbycarotidligation.AspreviouslyshownbyBiriny(1946,1947a)ligationofonecommoncarotidinrabbitscausesafallofbloodpressure,asmeasuredinthe*PhysiologicalInstitute,UniversityofUppsala.319 320R.J.Rosscentralarteryoftheear,oftheorderof30-40percent.andafallofintra-ocularpressureof15-20percent.ontheaffectedsideforaperiodofatleast24hours.Ifultra-filtrationisasignificantfactorsuchafallofbloodpressurecouldbeexpectedtocauseaconsiderablereductionintherateofaqueousflowandhenceintherateofentryofwaterintotheeye,aneffectwhichshouldresultinarise.intheureaconcentrationoftheaqueous.Unilateralcarotidligationwasaccordinglyperformeduponaseriesof.10rabbits,andtheureaconceptrationsoftheaqueousofthenormalandaffectedeyecompared.ExperimentalThecommoncarotidarterywastiedononesideinrabbitsunderpentabarbitoneanaesthesia,thevanLeersumlooptechniquebeingemployed.After24hours,whentheanim

alshadcompletelyrecovered,theywerekilledbydecapitationandtheaqueousremovedfrombotheyesasquicklyaspossible.Arterialbloodwascollectedfromtheneck.TABLEVITHEEFFECTOFREDUCINGTHEARTERIALPRESSUREBYCAROTIDOCCLUSIONUPONTHEUREACONCENTRATIONOFTHEAQUEOUSHUMOUROFR4BRITS.(Concentrationofureaexpressedasmg/100gH20).Si-deAqueousAqueousDifferenceDuplicatesRatioExpt.SiePlasmaonuntiedontiedTied-agreedAqueoustiedsidesideUntiedwithinPlasma45L80.962169.3+7mg%2%0.7647L74.859.966.6+7mg%2%0.8048L48.732.837.8+5mg%-3%0.6850L54.040.539.5-1mg%1%0.7451I65.852.248.0-4mg%2%0.7953R31.925.426.6+1mg%3%0.7955R48.534.030.6-3mg%1%0.7055R52.037.438.4+1mg%2%0.7257R71.950.353.6+3mg%2%0.7458R66.552.551.4-1mg%.3%0.79Mean0.75±0.02ResultsResultsarepresentedinTableVI.Theseshowthatloweringthesystemicbloodpressurebycarotidligationhasnosignificantinfluenceontheconcentrationofureaintheaqueous;theratioofconcentrationsofaqueous(occluded)toaqueous(control)-1,028±0*025. UUREAINAQUEOUSHUMOURDiscussionTheblood-aqueousbarrierhasbeenshownbykineticstudiestobepermeabletoureaalthoughtherateofpenetrationofthissubstanceintotheeyeisslowerthanthatofwater,ofothernon-electrolytessuchasethylalcohol,glucose,orglycerolandcorrespondswiththatofothernitrogenoussubstancessuchascreatinine,glycineoralanine.ThepermeabilityconstantsofthesesubstancesarecomparedinTableVII.Thisrelativelyslowrateofpenetrationissurprisinginviewoftherapiditywithwhichureapenetratesmembranesinotherparts.ofthebody,e.g.,itpenetratestheredcellenvelope35timesfasterthandoesglycerolandyetitsapparentrateofentryintotheeyeisonlyhalfthatofglycerol.IfentryintotheeyeoccurredbyTABLEVIICOMP'ARISONOFIPERMEABILITYCONSTANTSKAANDKV.SubstanceKAKVSpeciesReferenceWater...c.300-RabbitR

ecalculatedfromKinsey,GrantandCogan(1942).Ethylalcoholc.90-RabbitRecalculatedfromPalm(1947).Glucose...3411CatDavsonandDuke-Eider(1948).Glycerol-225CatDavson,Duke-Elder,Maurice,RossandWoodin(inpress).Creatinine14-1.9CatIbid.Glycine13.51.0CatIbid.Alanine12.708CatIbid.Urea...11.95.4Catultrafiltrationacrossasemipermeablemembranethroughlargewater-filledpores,non-electrolytesshouldhave-apermeabilityconstantwhichisproportionaltothesquarerootoftheirmolecularweights(DavsonandDanielli,1943).DavsonandDuke-Elder's(1948)studiesofthepermeabilityconstantsofcarbohydratessuggestthatthesesubstancespassintotheeyeatratesinverselyproportionaltotheirmolecularsize.Theureamoleculeisonlyone-thirdaslargeasthatofglucoseandyettheglucosemoleculeenterstheeyethreetimesasfastasurea,afactsuggestingthatinthecaseofureasomeactivitvotherthanaprocessofultrafiltration321- 322R.J.Rossisinvolved.Paracentesisofaqueousfromtheanteriorchambertemporarilyderangesthisselectivepermeabilityofthebarriersothattheureaconcentrationofthereformed"secondary"aqueousisatfirstequaltothatoftheplasmawater,slowlyfallingtonormalwithinthe-succeeding24hours.Theblood-vitreousbarrierhasbeenfouindtobeevenlesspermeabletour'eathanistheblood-aqueousbarrier,therespectivepermeabilityconstantsbeing54and119.Re-determinationoftheaqueous/plasmaandvitreous/plasmaconcentrationratioshasconfirmedpreviousobservationsthatadeficitoftheorderof20perqent.existsbetweentheintra-ocularfluidsandtheplasmawater;anaqueous/plasmaratioof076wasfoundinthecatandof075intherabbit:thevitreous/plasmaratiowas077inthecat.Theexistenceofthisdeficitintheintra-ocularfluidsmightindicatethatureawasenteringtheeyebyultrafiltrationandwasbeingremovedbyenteringifitothemetaboli

smofthelensorotherstructureswithintheeye.Thispossibilitvhasbeenexaminedbyacomparisonoftheaqueous/plasmaratiosofthenormalandtheaphakiceyeinrabbits,byinvitrostudiesofthelensandalsooftheexcisedeye,butnoevidenceforanyutilisationofureahasbeenfound.TherespectivecontributionsofultrafiltrationandsecretiontotheformationoftheaqueoushavebeenstudiedbyamethodduetoBArAny(1947b).Ifultrafiltrationwereanimportantmechanisminaqueousformationthen,followingKinseyandGrant's(1942)hypothesis,reductioninsystemicbloodpressurebyunilateralcarotidocclusionwouldcauseareductionintherateofultra-filtrationwhichwouldshowupasariseinthewreaconcentrationontheaffectedside.Sucharisecannotbedemonstratedexperi-mentally,fromwhichithasbeeninferredthatultrafiltrationplayslittlepartintheformationoftheaqueoushumour.TheseresultsareinagreementwiththefindingsofBar4ny(1947b)whofoundthatreductionofbloodpressurehadnoeffect.upontherateofentryonNa24intotheaqueous.Barany(1947c)laterfoundthatloweringthebloodpressurelikewisehadnoeffectontheosmoticpressureoftheaqueoussuchaswouldbeexpectedtooccurifultrafiltrationwereplayingadominantpartinaque-ousformation.Theseresultssuggestthatsomemechanismispresentatthebarriertoregulatetheentryoffluidintotheeyesoastomaintaintheaqueousflowconstantirrespectiveofthesystemicbloodpressure.Thedatapresentedinthispaperthusshowthattheblood-aqueousbarrieroffersconsiderableresistancetotheentryofurea322 UREAINAQUEOUSHUMOURintotheeyeandthatitsrateofpenetrationisindependentofthesystemicbloodpressure;theevidenceobtainedsuggeststhatureaenterstheeyebysomeprocessotherthansimpleultra-filtration.Summary(1)Theureaconcentrationintheaqueoushumourandthevitreousbodyhasbeenfoundtoberespectively76percent.and77p

ercent.ofthatoftheplasmawater.(2)Therateofpenetrationofureaintotheaqueousandvitreoushasbeenmeasuredandthecorrespondingpermeabilityconstantscalculated.Theseshowthatpenetrationintotheaqueousis-twiceasrapidasintothevitreousandindicatethattheblood-aqueousandblood-vitreousbarriersofferconsiderableresistancetothepassageofureafromthebloodtotheintra-ocularfluids.(3)Theureadeficitwithintheeyeisnotduetoutilisationbystructureswithintheeye.(4)Therateofpenetrationintotheaqueoushasbeenshowntobeindependentofthesystemicbloodpressureandtheevidencepresentedsuggeststhatthesubstanceistransferredacross-theblood-aqueousbarrierbyaprocessotherthansimpleultra-filtration.IamindebtedtoSirStewartDuke-ElderandDr.HughDavsonfortheirinterestandadvice.REFERENCESANDRESEN,K.L.G.(1921).-Biochem.Zeitschr.,116,266.ADLER,F.H.(1933).-Arch.ofOphthal.,10,11.BARANY,E.-H.(1946).-ActaOhthal.,24,337.(1947a).-Ibid.,25,81.(1947b).-ActaPhysiol.Scand.,13,55.(1947c).-Ibid.,13,81.BENHIAM.G.H.(1937).-Biochem.J.,31,1157.CONWAY,E.J.(1946)-Microdiffusionanalysisandvolumetricerror.Secondedition.London.DAVSON,H.andDANIELLI,J.F.(1943).-The-permeabilityofnaturalmembranes.CambridgeUniversityPress.andDUKE-ELDER,W.S.(1948).-J.Physiol.,107,141.DUKE-ELDER,W.S.,MAURICE.-D.M.,Ross,E.J.andWOODIN,A.M.-Ibid.,inpress.--andQUILLIAM,J.P.(194G).-Ibid.,98,141.DUKE-ELDER,W.S.(1927).-Biochem.J.,21,66.KINSEY,V.E.andGRANT,W.M.(1942).-J.Gen.Physiol.,26,119,131.andCOGAN,D.G.(1942).-Arch.ofOphthal.,27,242.andROBISON,P.(1946).-J.Biol.Chem.,162,325.MOORE,E.,SCHEIE,H.G.andADLER,F.H.(1942).-Arch.ofOfihthal.,27,317.PALM,E.(1947).-ActaOphthal.,25,139.SCHEIE,H.G.,MOORE,E.andADLER,F.H.(1943).Arch.ofOphthal.,30,70.WALKER,A.M.(1933).-J.Biol.Chem.,101,2