PURPOSE.To study the effect on outflow facility and outflow resistance of a nitinol microstent implanted into Schlemm's canal.METHODS. Using a constant pressure perfusion method, outflow facility and outflow resistance were measured in 26 pairs of dissected anterior segments from donated human eyes. Measurements were made at perfusion pressures of 10, 20, 30 and 40 mm Hg. The Hydrus Microstent was placed in Schlemm's canal of one eye and the contralateral eye underwent a sham procedure. Outflow facility and outflow resistance were measured again after the microstent implantation or sham procedure.RESULTS. The Hydrus Microstent significantly increased outflow facility from 0.33 6 0.17 lL/min/mm Hg to 0.52 6 0.19 lL/ min/mm Hg (P < 0.001). Outflow resistance was significantly reduced from 4.38 6 3.03 mm Hg/lL/min at baseline to 2.34 6 1.04 mm Hg/lL/min (P < 0.001) with the microstent. There was a linear correlation between outflow resistance at baseline and decrease in outflow resistance with the microstent (R 2 ¼ 0.89, P < 0.0001).CONCLUSIONS. The increase in outflow facility and decrease in resistance supports the potential use of the Hydrus Microstent as a surgical option to reduce intraocular pressure (IOP). The IOP-lowering effect may be higher in eyes with higher outflow resistance (and IOP) as compared with eyes with lower outflow resistance (and IOP). (Invest Ophthalmol Vis Sci.

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission.

First proposed as a specialized mode of release at sensory neurons possessing ribbon synapses, multivesicular release has since been described throughout the central nervous system. Many aspects of multivesicular release remain poorly understood. We explored mechanisms underlying simultaneous multivesicular release at ribbon synapses in salamander retinal rod photoreceptors. We assessed spontaneous release presynaptically by recording glutamate transporter anion currents (I A(glu) ) in rods. Spontaneous I A(glu) events were correlated in amplitude and kinetics with simultaneously measured miniature excitatory postsynaptic currents in horizontal cells. Both measures indicated that a significant fraction of events is multiquantal, with an analysis of I A(glu) revealing that multivesicular release constitutes $30% of spontaneous release events. I A(glu) charge transfer increased linearly with event amplitude showing that larger events involve greater glutamate release. The kinetics of large and small I A(glu) events were identical as were rise times of large and small miniature excitatory postsynaptic currents, indicating that the release of multiple vesicles during large events is highly synchronized. Effects of exogenous Ca 2þ buffers suggested that multiquantal, but not uniquantal, release occurs preferentially near Ca 2þ channels clustered beneath synaptic ribbons. Photoinactivation of ribbons reduced the frequency of spontaneous multiquantal events without affecting uniquantal release frequency, showing that spontaneous multiquantal release requires functional ribbons. Although both occur at ribbon-style active zones, the absence of cross-depletion indicates that evoked and spontaneous multiquantal release from ribbons involve different vesicle pools. Introducing an inhibitory peptide into rods to interfere with the SNARE protein, syntaxin 3B, selectively reduced multiquantal event frequency. These results support the hypothesis that simultaneous multiquantal release from rods arises from homotypic fusion among neighboring vesicles on ribbons and involves syntaxin 3B.