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Ester Reina-Torres, Leonie Herrnberger, Joseph M Sherwood, Ernst R Tamm, Darryl R Overby; The Influence of Plasmalemma Vesicle-Associated Protein on Conventional Outflow Facility in Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3543.
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© ARVO (1962-2015); The Authors (2016-present)
Plasmalemma Vesicle-Associated Protein (PLVAP) is necessary for fenestra formation in fenestrated endothelia. Schlemm’s canal (SC) has fenestra-like mini-pores of 60-80nm, and fewer SC mini-pores are observed in mice lacking PLVAP. As mini-pores may be precursors of micron-sized intracellular pores in SC endothelium, we hypothesize that PLVAP plays a role in modulating conventional outflow facility (C). We investigate the effect of PLVAP depletion on IOP and outflow facility, and additionally examine how C is affected by the actin-disrupting drug latrunculin B.
This project used wild type (WT: PLVAP+/+) and knock-down (KD: PLVAP-/+) mouse littermates, 9-12 weeks of age, on a C57/BL/N background. Both genders were used. IOP was measured by rebound tonometry on anesthetized mice. C was measured in enucleated eyes using the iPerfusion system optimized for mouse eyes. When evaluating the difference between WT and KD, one eye of each mouse was perfused with DBG (Dulbecco’s PBS + 5.5mM glucose). To assess the effect of latrunculin B in WT and KD, one eye was perfused with 1µM latrunculin B in DBG while the contralateral eye was perfused with DBG + vehicle. Statistical significance was determined by a customized weighted t-test.
The WT and KD mice had similar IOP at 11 weeks, 12.8 ± 2.2 mmHg (mean ± SD, n = 14) and 12.8 ±1.5 mmHg (n = 12) respectively. However, C was reduced by 31% in KD versus WT (p = 0.06; n = 14 KD; n = 12 WT). Eyes from WT mice perfused with 1µM latrunculin B had 25% higher C (p < 0.02; n = 7 pairs) relative to contralateral controls, whereas KD mice experienced a 62% increase (p < 0.0001; n = 7 pairs). There was no significant difference between eyes from WT and KD mice treated with latrunculin B (p > 0.9).
Facility was reduced in PLVAP-depleted mice, suggesting that PLVAP-containing mini-pores may contribute to outflow regulation. However, IOP was unaffected, possibly because fenestrae are necessary for aqueous humor production by ciliary process capillaries. Cytoskeletal disruption by latrunculin eliminated the influence of PLVAP, suggesting a cellular origin for the extra resistance in the PLVAP-depleted mice. Electron microscopy studies are necessary to examine the role of PLVAP in pore formation in SC.
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