A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: "young" (2-6 months), "middle-aged" (11-16 months), and "elderly" (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area on varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.

Evidence for Menopause as a Sex-Specific Risk Factor for Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive loss of visual function and retinal ganglion cells (RGC). Current epidemiological, clinical, and basic science evidence suggest that estrogen plays a role in the aging of the optic nerve. Menopause, a major biological life event affecting all women, coincides with a decrease in circulating sex hormones, such as estrogen. While 59% of the glaucomatous population are females, sex is not considered a risk factor for developing glaucoma. In this review, we explore whether menopause is a sex-specific risk factor for glaucoma. First, we investigate how menopause is defined as a sex-specific risk factor for other pathologies, including cardiovascular disease, osteoarthritis, and bone health. Next, we discuss clinical evidence that highlights the potential role of menopause in glaucoma. We also highlight preclinical studies that demonstrate larger vision and RGC loss following surgical menopause and how estrogen is protective in models of RGC injury. Lastly, we explore how surgical menopause and estrogen signaling are related to risk factors associated with developing glaucoma (e.g., intraocular pressure, aqueous outflow resistance, and ocular biomechanics). We hypothesize that menopause potentially sets the stage to develop glaucoma and therefore is a sex-specific risk factor for this disease.

Ovariectomy worsens visual function after mild optic nerve crush in rodents.

Glaucoma is the leading cause of irreversible blindness worldwide, and women represent roughly 60% of the affected population. Early menopause and estrogen signaling defects are risk factors for glaucoma. Recently, we found that surgical menopause exacerbated visual dysfunction in an ocular hypertension model of glaucoma. Here, we investigated if surgical menopause exacerbated visual dysfunction in a model of direct retinal ganglion cell (RGC) damage via optic nerve crush (ONC). Female Long Evans rats (n = 12) underwent ovariectomy (OVX) to induce surgical menopause or Sham surgery. Eight weeks post-surgery, baseline visual function was assessed via optomotor response. Afterwards, rats underwent monocular ONC. Visual function was assessed at 4, 8, and 12 weeks post-ONC. At 12 weeks, retinal function via electroretinography and retinal nerve fiber layer (RNFL) thickness via optical coherence tomography were measured. Visual acuity was reduced after ONC (p < 0.001), with surgical menopausal animals having 31.7% lower visual acuity than Sham animals at 12 weeks (p = 0.01). RNFL thinning (p < 0.0001) and decreased RGC function (p = 0.0016) occurred at 12 weeks in ONC groups. Surgical menopause worsens visual acuity after direct RGC damage using an ONC model. This demonstrates that surgical menopause plays a role in visual function after injury.

Using retinal function to define ischemic exclusion criteria for animal models of glaucoma.

Most animal models of glaucoma rely on induction of ocular hypertension (OHT), yet such models can suffer from high IOPs leading to undesirable retinal ischemia. Thus, animals with IOPs exceeding a threshold (e.g. > 60 mmHg) are often excluded from studies. However, due to the intermittent nature of IOP measurements, this approach may fail to detect ischemia. Conversely, it may also inappropriately eliminate animals with IOP spikes that do not induce ischemic damage. It is known that acute ischemia selectively impairs inner retinal function, which results in a reduced b-wave amplitude. Here, we explore the potential of using electroretinography (ERG) to detect ischemic damage in OHT eyes. 74 Brown Norway rats received a unilateral injection of magnetic microbeads to induce OHT, while contralateral eyes served as controls. IOP was measured every 2-3 days for 14 days after microbead injection. Retinal function was evaluated using dark-adapted bright flash ERG (2.1 log cd•s/m2) prior to, and at 7 and 14 days after, injection. We investigated two criteria for excluding animals: (IOP Criterion) a single IOP measurement > 60 mmHg; or (ERG Criterion) a b-wave amplitude below the 99.5% confidence interval for naïve eyes. 49 of 74 rats passed both criteria, 7 of 74 failed both, and 18 passed one criterion but not the other. We suggest that ERG testing can detect unwelcome ischemic damage in animal models of OHT. Since brief IOP spikes do not necessarily lead to ischemic retinal damage, and because extended periods of elevated IOP can be missed, such ERG-based criteria may provide more objective and robust exclusion criteria in future glaucoma studies.

Menopause exacerbates visual dysfunction in experimental glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3-4 months) and aged (9-10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). After six weeks, ocular hypertension (OHT) was induced unilaterally for a period of eight weeks. Four cohorts were successfully followed to eight weeks: young sham (n = 8), young OVX (n = 9), aged sham (n = 10), and aged OVX (n = 11) animals. Intraocular pressure (IOP) was monitored weekly in all groups. Prior to inducing OHT (baseline) and at four and eight weeks after inducing OHT, we assessed visual acuity via the optomotor response (OMR) and retinal structure using optical coherence tomography (OCT). OHT decreased the OMR in all cohorts. We found that spatial frequency thresholds decreased by 54% in OVX animals after OHT compared to sham animals after OHT, regardless of age (p < 0.001). We also found thinning of the retinal nerve fiber layer (RNFL) and loss of total retinal thickness after induction of OHT. Aged animals had more thinning of the RNFL and loss of total retinal thickness compared to young animals (p < 0.001). Overall, OHT caused significant changes in visual function and retinal structure. Observing that OVX in young and aged animals further decreased spatial frequency thresholds after OHT suggests that an estrogen deficiency may intensify visual impairment after OHT.

First delivery and ovariectomy affect biomechanical and structural properties of the vagina in the ovine model.

INTRODUCTION AND HYPOTHESIS: Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina. METHODS: We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group). We also harvested mid-vaginal and distal vaginal tissue to determine smooth muscle contractility and passive biomechanical properties, for morphometric assessment of the vaginal wall layers, to determine collagen and elastin content, and for immunostaining for α-smooth muscle actin and estrogen receptor-α. RESULTS: There were no regional differences in the nulliparous vagina. One year after the first vaginal delivery, stiffness and contractility of the distal vagina were decreased, whereas the elastin content increased. The mid-vagina of ovariectomized sheep was stiff, and its epithelium was thin and lacked glycogen. HRT decreased the stiffness of the mid-vagina by 45% but had no measurable effect on contractility or elastin content, and increased epithelial thickness and glycogen content. HRT also increased the epithelial thickness and glycogen content of the distal vagina. At this location, there were no changes in morphology or stiffness. CONCLUSION: In sheep, life events including delivery and ovariectomy affect the biomechanical properties of the vagina in a region-specific way. Vaginal delivery mainly affects the distal region by decreasing stiffness and contractility. HRT can reverse the increase in stiffness of the mid-vagina observed after surgical induction of menopause. These observations are in line with scanty biomechanical measurements in comparable clinical specimens.

Comparative Anatomy of the Ovine and Female Pelvis.

BACKGROUND: Pelvic organ prolapse affects half of vaginally parous women. Several animal models are used to study its pathophysiology and treatment. Sheep are interesting because they develop spontaneously prolapse with similar risk factors as women and can be used for vaginal surgery. This study describes ovine pelvis anatomy and compares it to women's pelvis to provide anatomical tools for translational researchers. METHODS: MRI, pelvic dissections, and histology were used for detailed macro- and microscopic analysis of relevant anatomical structures in 6 nulliparous ewes. RESULTS: Although sheep are quadrupeds, the gross and microscopic anatomies are similar to the female pelvis. Principal differences are the shape and its orientation, the absence of the sacrospinous ligament and the internal obturator. The levator ani (except for the puborectalis) and the coccygeus muscle are present, yet the latter is more developed - coinciding with the tail. The dimensions and morphology of the ovine vagina is comparable. The retropubic and the rectovaginal space are accessible transvaginally. There is a wide expression of estrogen receptors with low or absent immunoreactivity in the urethral epithelium, bladder, anus and internal anal sphincter. CONCLUSION: The ovine pelvic floor has many anatomical and ultrastructural similarities to the female pelvic floor.

Host reaction to vaginally inserted collagen containing polypropylene implants in sheep.

OBJECTIVE: We aimed to characterize the effect of vaginal or abdominal mesh insertion and of different collagen augmentation of polypropylene mesh in a sheep model. Outcome measures were passive and active biomechanical properties and semiquantitative morphometry. STUDY DESIGN: Forty-two Texel sheep were used: 6 were nonimplanted controls (n = 6), the rest were implanted with polypropylene mesh (n = 12; Avaulta Solo; Bard Medical, Covington, GA) or collagen-coated meshes: Avaulta Plus (n = 12; Bard Medical) and Ugytex (n = 12; Sofradim International, Trevoux, France). Through a single incision, the rectovaginal septum was dissected and a 35 × 35-mm mesh was sutured to the underlying tissues. Abdominally, a 50 × 50-mm mesh was laid over a primarily sutured full thickness 40-mm longitudinal incisional defect. Animals were explanted after 60 or 180 days (n = 6 per group). Outcome measures were passive biomechanics by biaxial tensiometry, active contractility of vaginal explants, and histologic evidence. RESULTS: Vaginal explants were 2.4 times stiffer compared with native vaginal tissue (P < .001), but without differences in comfort zone stiffness or slope of the load-elongation in the physiologic range between the products that were tested. Collagen coating was associated with a 16-fold reduction in contractile force at 180 days, compared with native vaginal tissue, both for Avaulta Plus (P = .032) and Ugytex (P = .015). Abdominal explants were 1.3-times stiffer compared with native abdominal wall tissue (P < .001) and were 1.9-times stiffer compared with vaginal explants. CONCLUSION: Vaginal mesh implantation yields less stiff explants compared with abdominal explants. Vaginal mesh implantation also alters the passive and active biomechanical properties compared with native vaginal tissues. Collagen matrices did not reduce the number of graft-related complications.

High-frequency micro-ultrasound: a novel method to assess external urethral sphincter function in rats following simulated birth injury.

AIMS: We evaluated external urethral sphincter (EUS) function using high-frequency micro-ultrasound (US) in rats that were either uninjured (Control, C) or underwent vaginal distension (VD) as a substitute for vaginal birth injury induced stress urinary incontinence (SUI). METHODS: Thirteen female nulliparous Sprague-Dawley rats of 12 weeks were divided into two groups, either C (n = 6) or VD (n = 7). Vaginal balloon distension was performed under pentobarbital anesthesia for 4 hours. Five days after the injury, all animals underwent US assessment of the urethra during high-rate bladder filling and urine leakage/voiding. Urinary leakage, the presence, absence, and pattern of EUS bursting during the voiding phase were registered, and pre-determined parameters of intercontraction interval (ICI), length of contraction (LOC), and rate of contraction (ROC) were registered. RESULTS: Our ultrasound findings consistently showed the presence of rhythmic EUS bursting in all of the C rats (6/6), which were absent in all VD rats (0/7). The mean of ROC, ICI, and LOC in C group were 3.02 ± 0.12 contractions/sec, 471.43 ± 17.9 msec, and 103.41 ± 3.28 msec, respectively. CONCLUSIONS: Pre-determined parameters of LOC, ICI, and ROC during US provide objective and measurable data on EUS function. US showed the total disappearance of EUS bursting in the VD group as compared to the C group. These results indicate that ultrasound testing may become a valuable non-invasive tool in future translational studies to investigate SUI/urethral function in rat models.

Three-dimensional analysis of implanted magnetic-resonance-visible meshes.

OBJECTIVE: Our primary objective was to develop relevant algorithms for quantification of mesh position and 3D shape in magnetic resonance (MR) images. METHODS: In this proof-of-principle study, one patient with severe anterior vaginal wall prolapse was implanted with an MR-visible mesh. High-resolution MR images of the pelvis were acquired 6 weeks and 8 months postsurgery. 3D models were created using semiautomatic segmentation techniques. Conformational changes were recorded quantitatively using part-comparison analysis. An ellipticity measure is proposed to record longitudinal conformational changes in the mesh arms. The surface that is the effective reinforcement provided by the mesh is calculated using a novel methodology. The area of this surface is the effective support area (ESA). RESULTS: MR-visible mesh was clearly outlined in the images, which allowed us to longitudinally quantify mesh configuration between 6 weeks and 8 months after implantation. No significant changes were found in mesh position, effective support area, conformation of the mesh's main body, and arm length during the period of observation. Ellipticity profiles show longitudinal conformational changes in posterior arms. CONCLUSIONS: This paper proposes novel methodologies for a systematic 3D assessment of the position and morphology of MR-visible meshes. A novel semiautomatic tool was developed to calculate the effective area of support provided by the mesh, a potentially clinically important parameter.

Biomechanics of the rat vagina during pregnancy and postpartum: a 3-dimensional ultrasound approach.

INTRODUCTION AND HYPOTHESIS: The vagina and surrounding structures have been shown to remodel during pregnancy. Our objective was to characterize the biomechanical properties of the vagina in the rodent model in vivo utilizing three-dimensional (3D) ultrasound. METHODS: The vagina was visualized by ultrasound after distention by increasing pressures throughout pregnancy (15 and 18 days) and after vaginal delivery (7 and 30 days postpartum) of six longitudinally followed rodents. The pelvic floor compliance and vaginal cross-sectional area of the proximal, middle, and distal vagina were compared with those of nulliparous control animals (n = 8). RESULTS: The compliance of the pelvic floor increased 3.5- and 5.4-fold at days 15 and 18 of pregnancy respectively (p < 0.05). The compliance of the pelvic floor decreased 7 days postpartum, and it continued to decrease after vaginal delivery through the 30 day time point. Using 3D ultrasound, we could characterize the remodeling of the vagina throughout pregnancy and after vaginal delivery. We could reconstruct the vaginal wall cross-sectional area and found the distal vaginal wall throughout pregnancy to be distended more than the proximal and middle regions. CONCLUSIONS: The observed changes in vaginal area may improve our understanding of which areas are at risk of injury during delivery. Further, 3D ultrasound allowed the determination of the in vivo biomechanical properties of the vagina. This image modality is beneficial for characterizing the in vivo properties of the vagina and surrounding pelvic support longitudinally within an animal.

Mesh contraction: in vivo documentation of changes in apparent surface area utilizing meshes visible on magnetic resonance imaging in the rabbit abdominal wall model.

INTRODUCTION AND HYPOTHESIS: Our aim was to analyze the apparent contraction of meshes in vivo after abdominal wall reconstruction and evaluate histological and biomechanical properties after explantation. METHODS: Nine New Zealand female rabbits underwent repair of two full-thickness 25 × 30-mm midline defects in the upper and lower parts of the abdomen. These were primarily overlaid by 35 × 40-mm implants of a polyvinylidene fluoride (PVDF) DynaMesh (n = 6) or polypropylene meshes Ultrapro (n = 6) and Marlex (n = 6). Edges of the meshes were secured with iron(II,III) oxide (Fe(3)O(4))-loaded PVDF sutures. Magnetic resonance images (MRIs) were taken at days 2, 30 and 90 after implantation. The perimeter of the mesh was traced using a 3D spline curve. The apparent surface area or the area within the PVDF sutures was compared with the initial size using the one-sample t test. A two-way repeat analysis of variance (ANOVA) was used to compare the apparent surface area over time and between groups. RESULTS: PVDF meshes and sutures with Fe(3)O(4) could be well visualized on MRI. DynaMesh and Marlex each had a 17 % decrease in apparent surface area by day 2 (p < 0.001 and p = 0.001), respectively, which persisted after day 90. Whereas there was a decrease in apparent surface area in Ultrapro, it did not reach significance until day 90 (p = 0.01). Overall, the apparent surface area decreased 21 % in all meshes by day 90. No differences in histological or biomechanical properties were observed at day 90. CONCLUSIONS: There was a reduction in the apparent surface area between implantation and day 2, indicating that most mesh deformation occurs prior to tissue in-growth.

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intraocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: 'young' (2-6 months), 'middle-aged' (11-16 months), and 'elderly' (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area to varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs, and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.

A method for analyzing AFM force mapping data obtained from soft tissue cryosections.

Atomic force microscopy (AFM) is a valuable tool for assessing mechanical properties of biological samples, but interpretations of measurements on whole tissues can be difficult due to the tissue's highly heterogeneous nature. To overcome such difficulties and obtain more robust estimates of tissue mechanical properties, we describe an AFM force mapping and data analysis pipeline to characterize the mechanical properties of cryosectioned soft tissues. We assessed this approach on mouse optic nerve head and rat trabecular meshwork, cornea, and sclera. Our data show that the use of repeated measurements, outlier exclusion, and log-normal data transformation increases confidence in AFM mechanical measurements, and we propose that this methodology can be broadly applied to measuring soft tissue properties from cryosections.

Voluntary exercise preserves visual function and reduces inflammatory response in an adult mouse model of autosomal dominant retinitis pigmentosa.

Whole-body physical exercise has been shown to promote retinal structure and function preservation in animal models of retinal degeneration. It is currently unknown how exercise modulates retinal inflammatory responses. In this study, we investigated cytokine alterations associated with retinal neuroprotection induced by voluntary running wheel exercise in a retinal degeneration mouse model of class B1 autosomal dominant retinitis pigmentosa, I307N Rho. I307N Rho mice undergo rod photoreceptor degeneration when exposed to bright light (induced). Our data show, active induced mice exhibited significant preservation of retinal and visual function compared to inactive induced mice after 4 weeks of exercise. Retinal cytokine expression revealed significant reductions of proinflammatory chemokines, keratinocyte-derived chemokine (KC) and interferon gamma inducible protein-10 (IP-10) expression in active groups compared to inactive groups. Through immunofluorescence, we found KC and IP-10 labeling localized to retinal vasculature marker, collagen IV. These data show that whole-body exercise lowers specific retinal cytokine expression associated with retinal vasculature. Future studies should determine whether suppression of inflammatory responses is requisite for exercise-induced retinal protection.

Pentosan Polysulfate Sodium Causes Diminished Function and Subtle Morphological Changes in Retina and RPE of Mice.

Purpose: There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated with interstitial cystitis. We tested whether PPS treatment of mice injures RPE or retina to provide insight into the etiology of the human condition. Methods: Mice were fed PPS-supplemented chow over 14 months. RPE and retinal function was assessed by electroretinography (ERG) regularly. Following euthanasia, one eye was used for sagittal sectioning and histology, the contralateral for RPE flatmounting. ZO-1 positive RPE cell borders were imaged using confocal microscopy and cell morphology was analyzed using CellProfiler. Results: After 10 months of PPS treatment, we observed diminution of mean scotopic c-wave amplitudes. By 11 months, we additionally observed diminutions of mean scotopic a- and b-wave amplitudes. Analysis of flatmounts revealed altered RPE cell morphology and morphometrics in PPS-treated mice, including increased mean en face cell area and geometric eccentricity, decreased RPE cell solidity and extent, and cytosolic translocation of alpha-catenin, all markers of RPE cell stress. Sex and regional differences were seen in RPE flatmount measures. Shortened photoreceptor outer segments were also observed. Conclusions: PPS treatment reduced RPE and later retina function as measured by ERG, consistent with a primary RPE injury. Post-mortem analysis revealed extensive RPE pleomorphism and polymegathism and modest photoreceptor changes. We conclude that PPS treatment of mice causes slowly progressing RPE and photoreceptor damage and thus may provide a useful model for some retinal pathologies.

Aging and intraocular pressure homeostasis in mice.

Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma.

Characterizing the ex vivo textile and structural properties of synthetic prolapse mesh products.

INTRODUCTION AND HYPOTHESIS: The use of polypropylene meshes for surgical repair of pelvic organ prolapse (POP) has been limited by complications, including mesh exposure, encapsulation, and pain. Numerous products are available with a wide array of textile and structural properties. It is thought that complications may be related, in part, to mesh structural properties. However, few descriptions of these properties exists to directly compare products. The aim of this study was to determine the textile and structural properties of five commonly used prolapse mesh products using a ball-burst failure protocol. METHODS: Porosity, anisotropic index, and stiffness of Gynemesh PS (n = 8), the prototype polypropylene mesh for prolapse repair, was compared with four newer-generation mesh produces: UltraPro (n = 5), SmartMesh (n = 5), Novasilk (n = 5), and Polyform (n = 5). RESULTS: SmartMesh was found to be the most porous, at 78 % ± 1.4 %. This value decreased by 21 % for Gynemesh PS (p < 0.001), 14 % for UltraPro and Novasilk (p < 0.001), and 28 % for Polyform (p < 0.001). Based on the knit pattern, SmartMesh and Polyform were the only products considered to be geometrically isotropic, whereas all other meshes were anisotropic. Comparing the structural properties of these meshes, Gynemesh PS and Polyform were the stiffest: 60 % and 42 % stiffer than SmartMesh (p < 0.001) and Novasilk (p < 0.001), respectively. However, no significant differences were found between these two mesh products and UltraPro. CONCLUSIONS: Porosity, anisotropy, and biomechanical behavior of these five commonly used polypropylene mesh products were significantly different. This study provides baseline data for future implantation studies of prolapse mesh products.

Changes in the rheological behavior of the vagina in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse is a common condition impacting the quality of life of millions of women worldwide. Although vaginal estrogen is widely used in women with prolapse, little is known regarding estrogen's benefits on the biomechanical properties of vaginal tissue. Here, we aimed to examine the effect of prolapse on the biomechanical properties of the vagina and determine alterations in vaginal mechanics in the presence and absence of hormone therapy (HT). METHODS: We characterized the viscoelastic properties of vaginal biopsies from age-matched premenopausal women without (n = 12) and with prolapse (n = 8) and postmenopausal women with prolapse on (n = 18) and off HT (n = 9). Utilizing a single-lap shear testing protocol, full-thickness anterior vaginal biopsies were subjected to ±10% shear strain over a range of frequencies (1-90 Hz). This applied energy is either dissipated (viscous) or stored (elastic) as a function of frequency due to compositional or structural differences in the tissue. RESULTS: Prolapsed tissue was more stiff (higher complex modulus) under shear deformation resulting from increases in both elastic (elastic modulus) and viscous (loss modulus) contributions, with non-prolapsed premenopausal women being the least stiff. Postmenopausal women with prolapse currently on HT were the most stiff of all the groups. CONCLUSIONS: These data suggest that prolapsed tissue has an increased elastic contribution likely resulting from changes in biochemical constituents, and hormones increase the viscous contribution of prolapsed tissue. Overall, this study design characterized the viscoelastic properties of vaginal biopsies and may be utilized to conduct longitudinal studies to better understand the mechanisms of prolapse development and progression.

Development of an Automated Electroretinography Analysis Approach.

Purpose: Electroretinography (ERG) is used to assess retinal function in ophthalmology clinics and animal models of ocular disease; however, analyzing ERG waveforms can be a time-intensive process with interobserver variability. We developed ERGAssist, an automated approach, to perform non-subjective and repeatable feature identification ("marking") of the ERG waveform. Methods: The automated approach denoised the recorded waveforms and then located the b-wave after applying a lowpass filter. If an a-wave was present, the lowpass filter wave was also used to help locate the a-wave, which was considered the initial large negative response after the flash stimuli. Oscillatory potentials (OPs) were found using a bandpass filter on the denoised waveform. We used two cohorts. One was a Coherence cohort that consisted of ERGs with eight dark-adapted and three light-adapted stimuli in Brown Norway rats (-6 to 1.5 log cd·s/m2). The Verification cohort consisted of control and diabetic (DM) Long Evans rats. We examined retinal function using a five-step dark-adapted protocol (-3 to 1.9 log cd·s/m2). Results: ERGAssist showed a strong correlation with manual markings of ERG features in our Coherence dataset, including the amplitudes (a-wave: r2 = 0.99; b-wave: r2 = 0.99; OP: r2 = 0.92) and implicit times (a-wave: r2 = 0.96; b-wave: r2 = 0.90; OP: r2 = 0.96). In the Verification cohort, both approaches detected differences between control and DM animals and found longer OP implicit times (P < 0.0001) in DM animals. Conclusions: These results provide verification of ERGAssist to identify features of the full-field ERG. Translational Relevance: This ERG analysis approach can increase the rigor of basic science studies designed to investigate retinal function using full-field ERG. To aid the community, we have developed an open-source graphical user interface (GUI) implementing the methods presented.