To probe the underlying biology associated with segmental AHO, biochemical and genetic studies were performed. Regions of high and low tracer accumulation could be isolated in mouse and probed by immunofluorescence . RT-PCR demonstrated increased versican (a large extracellular matrix proteoglycan) levels in low flow regions. Quantitative PCR arrays in enucleated human eyes demonstrated alterations in several extracellular matrix genes and their regulatory proteases . Using mouse models, segmental localization of fluorescent tracers in the TM of wild-type mice was abolished in the matricellular secreted protein acidic and rich in cysteine (SPARC) mutant . Distally, fluorescein microspheres could be seen past SC in the mouse as well .