Are you Sabrina Kuespert?

Claim your profile

Publications (3)8.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: The trabecular meshwork (TM) outflow pathways of the aqueous humor show an increase in extracellular matrix in patients with primary open-angle glaucoma (POAG). The increase in TM extracellular matrix appears to be caused by transforming growth factor-β signaling and its downstream mediator connective-tissue growth factor (CTGF). Here we studied whether treatment with the prostaglandin F2α analog fluprostenol modulates the CTGF-mediated increase of the TM extracellular matrix. Methods: Human TM cells from 3 different donors were treated with CTGF (50 ng/mL) and/or fluprostenol (10(-6) M and 10(-7) M) and were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting. Cell supernatants of the treated cells were analyzed by zymography. Results: Treatment with CTGF induced the expression and synthesis of CTGF, fibronectin, collagen type IV and VI, while treatment with fluprostenol alone had no effects. The effects of CTGF were blocked by 1-h pretreatment with fluprostenol in a dose-dependent manner. Treatment with fluprostenol or combined fluprostenol/CTGF induced the activity of matrix metalloproteinase 2 (MMP2) in TM cells, whereas treatment with CTGF alone had no effects on MMP2 activity. Conclusions: Fluprostenol blocks the fibrotic effects of CTGF on human TM cells and increases the activity of MMP2. Both effects have the distinct potential to attenuate a CTGF-mediated increase in TM extracellular matrix in patients with POAG and any effects on TM outflow resistance that may result from that.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014; · 1.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasmalemmal vesicle-associated protein (PLVAP, PV-1) is specifically expressed in endothelial cells in which it localizes to diaphragms of fenestrae, caveolae, and transendothelial channels. To learn about its function, we generated mutant mice that lack PLVAP. In a C57BL/6N genetic background, homozygous Plvap-deficient embryos die before birth and suffer from subcutaneous edema, hemorrhages, and defects in the vascular wall of subcutaneous capillaries. In addition, hearts of Plvap (-/-) embryos show ventricular septal defects and thinner ventricular walls. In wild-type embryos, PLVAP and caveolae with a stomatal diaphragm are present in endothelial cells of subcutaneous capillaries and endocardium, while a diaphragm is missing in caveolae of Plvap (-/-) littermates. Plvap (-/-) mice in a mixed C57BL/6N/FVB-N genetic background are born and survive at the most for 4 weeks. Capillaries of exocrine and endocrine pancreas and of kidney peritubular interstitium were investigated in more detail as examples of fenestrated capillaries. In these vascular beds, Plvap (-/-) mice show a complete absence of diaphragms in fenestrae, caveolae, and transendothelial channels, findings which are associated with a substantial decrease in the number of endothelial fenestrae. The changes in the capillary phenotype correlate with a considerable retardation of postnatal growth and anemia. Plvap (-/-) mice provide an animal model to clarify the specific functional role of endothelial fenestrae and their contribution to passage of water and solutes in different organs.
    Histochemie 07/2012; 138(5):709-24. · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The most critical risk factor for optic nerve damage in cases of primary open-angle glaucoma (POAG) is an increased intraocular pressure (IOP) caused by a resistance to aqueous humor outflow in the trabecular meshwork (TM). The molecular pathogenesis of this increase in outflow resistance in POAG has not yet been identified, but it may involve transforming growth factor TGF-β2, which is found in higher amounts in the aqueous humor of patients with POAG. Connective tissue growth factor (CTGF) is a TGF-β2 target gene with high constitutive TM expression. In this study, we show that either adenoviral-mediated or transgenic CTGF overexpression in the mouse eye increases IOP and leads to optic nerve damage. CTGF induces TM fibronectin and α-SMA in animals, whereas actin stress fibers and contractility are both induced in cultured TM cells. Depletion of CTGF by RNA interference leads to a marked attenuation of the actin cytoskeleton. Rho kinase inhibitors cause a reversible decline in the IOP of CTGF-overexpressing mice to levels seen in control littermates. Overall, the effects of CTGF on IOP appear to be caused by a modification of the TM actin cytoskeleton. CTGF-overexpressing mice provide a model that mimics the essential functional and structural aspects of POAG and offer a molecular mechanism to explain the increase of its most critical risk factor.
    American Journal Of Pathology 04/2012; 180(6):2386-403. · 4.60 Impact Factor