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J. Gottanka, C.R. Ethier, D. Chan, E. Lutjen-Drecoll; Effects of Tgf-ß2 on Outflow Facility and Trabecular Meshwork Morphology in Human Eyes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1165.
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Purpose: Concentrations of TGF-ß2 are known to be elevated in the aqueous humor of POAG patients. Here we investigate the effects of perfused TGF-ß2 on outflow facility and trabecular meshwork morphology in cultured human anterior eye segments. Methods: Ostensibly normal paired human eyes were perfused at constant flow (Q=2.5 µl/min) using the anterior segment organ culture system. After stable baseline facility was achieved (typically 3-5 days), the perfusion medium of the experimental eye was supplemented with 3 ng/ml of activated human recombinant TGF-ß2 and facility was measured for at least another 8 days. Eyes were then fixed at pressure, processed for transmission electron microscopy, and morphometrically analyzed to quantify filtering area of Schlemm’s canal (length of patent Schlemm’s canal) and extracellular material in the cribriform region. Results: TGF-ß2 perfusion caused a net 29 ± 11% (mean ± SEM) reduction in outflow facility after 8 days (P = 0.03; n= 8 pairs with good histology and facility). Increased extracellular fibrillar material was seen in treated and control eyes, with greater accumulation in treated eyes. In TGF-ß2 treated eyes, the length of the inner wall of SC was shortened by 24 ± 21% (P=0.02). Due to a higher amount of fibrillar material under the inner wall the remaining free filtering area was decreased by 33 ± 24% (P<0.01) if compared to the free filtering area of the contralateral control eyes. Conclusions: In the organ culture system TGF-ß2 reduced outflow facility, an effect consistent with increased amounts of extracellular matrix of the trabecular meshwork, particularly in the cribriform region. If these results can be extrapolated to the in vivo situation, elevated levels of TGF-ß2 in the aqeous humor of POAG patients could be pathogenic for changes in extracellular material in the outflow pathways and reduced outflow facility. Financial support: DFG SFB 539 (ELD), CIHR 10051 (CRE)
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