ischaracterizedbythedeathofretinal ganglioncells, leadingtoadeformationof theopticnerve, knownasglaucomatous cupping, andprogressivelossofthevisual field. Thisdiseaseisalsooftenassociated withelevatedintraocularpressure (IOP). Currenttherapiesinclude medicationsor surgeriesaimedatloweringthispressure, although the pathophysiological mechanisms by which elevated IOPleadstoneuronaldamagein glaucoma are unknown. Furthermore, glaucomais often asymptomaticfor an extended time period, andthereforeless than50% ofitsvictimsareaware oftheir disease. New diagnostic markersandtreatmentapproaches are desperately needed. Inthis issue, Wangetal. 1identifythecell-adhesion molecule endothelial leukocyte-adhesion molecule-1 (ELAM-1orE-selectin) asthefirst molecular markerofhumanglaucoma, andalsoprovidenewinsightintodiseasepathogenesis. In manyglaucomacases, elevatedIOPdevelopsasaresultof abnormally high resistance to drainageofaqueoushumor, afluid producedbytheciliarybodyofthe eyethatfiltersintothe blood throughtheoutflowsystem. The eye’soutflowsystem (Fig. 1) consists of aseries of endothelialcell–linedstructureswhichinclude thetrabecular meshwork (TM), Schlemm’scanal (SC), servingasa collectorvesselleadingtotheepiscleralvenoussystem, andtheepiscleralvenoussystem. Inhumans, theTMis madeupofcollagen beamscoveredbyendothelial-like cells. The space between the beamsisfilled withextracellular material/matrix (ECM). Aqueous humorfiltersthroughthe TM, crossestheSCcellwallandeventuallyleavestheeyebytheepiscleralvenoussystem. Inthenormaleye, theregionofmaximal resistancetoaqueoushumoroutflowincludestheperipheraljuxtacanaliculartrabecular meshwork (JTM), whichisadjacent toSCandtheinnerwallofSC (Fig. 1). The JTMhasnocollagenbeamsandconsistsof severallayersofcellsimmersedinECM. In differentformsofglaucoma, elevatedIOP maybeattributedtoanatomicalobstruction oftheaqueousoutflowpathwayorabnormaldepositionofECMleadingtoareduced filtrationcapacity. Otherpossiblecausesincludechangesintheconnectionsbetween TMendothelialcells, reorganizationsofthe cytoskeletonthataltertheshapeofTMcells orlossofTMcellsandpartialcollapseofthe trabecularbeamsasaresultofaging, oxidativeinsultandproteinaseaction. Thesestructuralabnormalitiesleadingto IOParelikelytodevelopasaresultof changesinthegeneandproteinexpression patternsbycellularcomponents of the outflow pathway. Mutationsingenesencoding myocilin (MYOC/TIGR), a cytochromeP450enzyme (CYP1B1) andseveraltranscriptionfactors (FKHL7, PITX2, LMX1B and PAX6) havebeenlinkedtoglaucoma2. However, these mutations accountforonlyasmallfraction ofglaucomacases. Asfamilyhistoryisariskfactor, itisclearthat othergenesinvolvedinglaucoma pathogenesisarelikelytobeidentified. Todate, nospecificmolecular markers for distinguishing betweennormalandglaucomatousTMhavebeenidentified. Cell-adhesion molecules are key components of biological structuresinvolvedinfluidcontainment and transport. Expressionofthese moleculesis typicallyupregulatedinresponse tocellularstressagentsimplicated invasculardisease. Wangetal. 1 investigatedtheroleofcell-adhesion moleculesintheaqueous outflowpathways. Usingnormal andglaucomatouseyesfromcadaversandacollectionofantibodies that recognize vascular endothelial cell-adhesion molecules, theauthorscomparedexpression of these molecules between normal and glaucomatous eyes. Theyfoundthat although expression of the cell-adhesion molecule ELAM-1 couldnotbedetectedinnormal eyes, it was constitutively expressedintheSCandJTMofglaucomatouseyes …