Interactions between endothelia of the trabecular meshwork and of Schlemm’s canal: a new insight into the regulation of aqueous outflow in the eye

Trans Am Ophthalmol Soc 12/2005; 103.
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Available from: Michael Brownstein, Jun 30, 2015
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    ABSTRACT: Aqueous humor is actively produced in the ciliary epithelium of the anterior chamber and has important functions for the eye. Under normal physiological conditions, the inflow and outflow of the aqueous humor are tightly regulated, but in the pathologic state this balance is lost. Aqueous outflow involves structures of the anterior chamber and experiences most resistance at the level of the trabecular meshwork (TM) that acts as a filter. The modulation of the TM structure regulates the filter and its mechanism remains poorly understood. Proteomic analyses have identified cochlin, a protein of poorly understood function, in the glaucomatous TM but not in healthy control TM from human cadaver eyes. The presence of cochlin has subsequently been confirmed by Western and immunohistochemical analyses. Functionally, cochlin undergoes multimerization induced by shear stress and other changes in the microenvironment. Cochlin along with mucopolysaccharide deposits has been found in the TM of glaucoma patients and in the inner ear of subjects affected by the hearing disorder DNFA9, a late-onset, progressive disease that also involves alterations in fluid shear regimes. In vitro, cochlin induces aggregation of primary TM cells suggesting a role in cell adhesion, possibly in mechanosensation, and in modulation of the TM filter.
    Progress in Retinal and Eye Research 10/2007; 26(5):453-69. DOI:10.1016/j.preteyeres.2007.06.002 · 8.73 Impact Factor
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    ABSTRACT: To evaluate the possible correlation between the visual field defects in patients with primary open-angle glaucoma (POAG) and the expression and enzymatic activity of nitric oxide synthase (NOS) isoenzymes and nitrotyrosine in trabecular meshwork (TM) samples. TM specimens were collected from 146 patients with POAG by using standard filtration surgery. Visual field defects were evaluated by perimetry. Expression of endothelial (e)NOS and inducible (i)NOS were evaluated by quantitative RT-PCR. Constitutive (Ca2+-dependent) and iNOS (Ca2+-independent) activities were measured by the conversion of L-[14C]-arginine to L-[14C]-citrulline. In four TM specimens from POAG-affected eyes and in three human donor control eyes, 3-nitrotyrosine was localized by immunohistochemistry. The marker of lipid peroxidation malondialdehyde (MDA) was measured by the thiobarbituric acid test in samples of aqueous humor (AH) from 48 patients with either POAG or cataracts. The results showed an upregulation of iNOS and a downregulation of calcium-dependent NOS correlated with visual field defects. Expression and activity of iNOS increased in parallel with visual field defects. However, constitutive activity decreased as the visual field defect increased. Nitrotyrosine was observed only in the cells of the TM specimens from eyes with severe POAG. The increased expression and activity of iNOS in the TM of patients with POAG are proportional to the visual field defect and could lead to the increased of nitrotyrosine levels which may serve as marker of oxidative stress in the progression of cell death of the TM in POAG.
    Investigative Ophthalmology &amp Visual Science 07/2008; 49(6):2506-11. DOI:10.1167/iovs.07-1363 · 3.40 Impact Factor
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    ABSTRACT: This study aimed to assess vascular endothelial function in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) by measuring: (a) endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery, and (b) circulating endothelial progenitor cells, which are believed to support the integrity of the vascular endothelium. We enrolled 25 patients with OHT, 23 with POAG and 26 control subjects, all of whom were aged < 65 years and had no medical history of cardiovascular disease or cardiovascular risk factors. All subjects underwent a complete ophthalmological examination, biochemistry study, assessment of cardiovascular parameters, brachial artery ultrasound assessment of endothelium-dependent FMD, generic circulating progenitor cell (CPC) and circulating endothelial progenitor cell (EPC) count with the use of flow cytometry. Flow-mediated vasodilation values differed significantly in OHT (4.5 +/- 1.1%; p = 0.021) and POAG (4.0 +/- 0.9%; p = 0.003) patients compared with controls (7.7 +/- 0.8%). The CD34(+) KDR(+) EPC count was markedly lower in OHT (28.0 +/- 5.0; p < 0.001) and POAG (24.3 +/- 3.4; p < 0.001) patients compared with controls (73.1 +/- 8.1). Neither FMD not EPCs differed significantly between OHT and POAG patients. No significant differences in CPC count or cardiovascular parameters were found among OHT or POAG patients and controls. The levels of CD34(+) KDR(+) EPCs were directly correlated (p = 0.043) with FMD, and inversely correlated (p = 0.032) with baseline intraocular pressure in OHT and POAG patients. Both OHT and POAG patients without cardiovascular risk factors have previously unreported severely reduced circulating EPCs and reduced FMD, both of which are indicators of endothelial dysfunction and increased risk of cardiovascular events.
    Acta ophthalmologica 06/2009; 88(1):135-41. DOI:10.1111/j.1755-3768.2009.01573.x · 2.84 Impact Factor
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