Dataset Information

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

ABSTRACT: The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ?1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

SUBMITTER: Vahabikashi A

PROVIDER: S-EPMC6936716 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

Vahabikashi Amir A Gelman Ariel A Dong Biqin B Gong Lihua L Cha Elliott D K EDK Schimmel Margit M Tamm Ernst R ER Perkumas Kristin K Stamer W Daniel WD Sun Cheng C Zhang Hao F HF Gong Haiyan H Johnson Mark M

Proceedings of the National Academy of Sciences of the United States of America 20191205 52

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize fl ...[more]

PMID: 31806762

Similar Datasets

Project description:PurposeTo examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere.DesignProspective, nonrandomized, case-control study.ParticipantsThirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls.MethodsNormal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed.Main outcome measuresTotal and hemispheric RS, RBF, RNFL, and GCC values.ResultsThe total RBF (34.6±12.2 μl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 μl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 μl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 μm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 μm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 μl/minute), RNFL (103.7 ± 20.6 μm), and GCC (83.6 ± 10.1 μm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 μl/minute, 124.8 ± 9.6 μm, and 96.1 ± 5.7 μm, respectively).ConclusionsIn glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

Project description:PurposeTo investigate the structural and clinical characteristics of peripapillary retinoschisis observed in glaucomatous eyes using spectral-domain optical coherence tomography (SD-OCT).MethodsCircumpapillary retinal nerve fiber layer (cpRNFL) and macular cross-hair SD-OCT scans and infrared fundus images of the glaucoma patients from the Investigating Glaucoma Progression Study (IGPS) and healthy volunteers were reviewed. Optic disc images obtained using enhanced depth imaging (EDI) SD-OCT were also evaluated. The structural characteristics and clinical course of the retinoschisis associated with glaucoma were investigated.ResultsTwenty-five retinoschisis areas were found in 22 of the 372 patients (5.9%) included in the IGPS, and in 1 area in 1 of 187 healthy control subjects (0.5%). In the 22 glaucomatous eyes with retinoschisis, the schisis was attached to the optic disc and overlapped with the retinal nerve fiber layer (RNFL) defect. The RNFL was the layer most commonly affected by the retinoschisis, either alone or together with other deeper layers. Acquired optic disc pit was identified in 8 eyes on disc photography and/or B-scan images obtained by EDI SD-OCT. Spontaneous resolution of this condition was observed in nine eyes. No retinal detachment or macular involvement of the retinoschisis was observed in any of the eyes. Multivariate analysis showed a significant influence of a higher intraocular pressure at SD-OCT scanning on the presence of retinoschisis (Odds ratio = 1.418, P = 0.001).ConclusionsThe present study investigated 22 cases of peripapillary retinoschisis in glaucomatous eyes. The retinoschisis was attached to the optic nerve and topographically correlated with RNFL defect. It often resolved spontaneously without causing severe visual disturbance. Care should be taken not to overestimate the RNFL thickness in eyes with retinoschisis, and also not to misinterpret the resolution of retinoschisis as a rapid glaucomatous RNFL deterioration.

Dataset Information

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

Publications

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets