Safety and Effectiveness of Smooth Incision Lenticular Keratomileusis (SILK) Using the ELITA Femtosecond Laser System for Correction of Myopic and Astigmatic Refractive Errors.

Purpose: To evaluate visual outcomes following the Smooth Incision Lenticular Keratomileusis (SILK) procedure for correction of myopic refractive errors with and without astigmatism, using the ELITA Femtosecond Laser System.

Patients And Methods: A prospective, multicenter, single-arm, open-label clinical study was conducted. Eighty-five myopic subjects (n = 170 eyes), aged 18 years or older, with manifest refractive spherical equivalent (MRSE) up to -12.

Eye-specific 3D modeling of factors influencing oxygen concentration in the lamina cribrosa.

Our goal was to identify the factors with the strongest influence on the minimum lamina cribrosa (LC) oxygen concentration as potentially indicative of conditions increasing hypoxia risk. Because direct measurement of LC hemodynamics and oxygenation is not yet possible, we developed 3D eye-specific LC vasculature models. The vasculature of a normal monkey eye was perfusion-labeled post-mortem.

Lamina cribrosa vessel and collagen beam networks are distinct.

Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labeled by perfusion post-mortem.

So-Called Lamina Cribrosa Defects May Mitigate IOP-Induced Neural Tissue Insult.

Purpose: The prevailing theory about the function of lamina cribrosa (LC) connective tissues is that they provide structural support to adjacent neural tissues. Missing connective tissues would compromise this support and therefore are regarded as "LC defects", despite scarce actual evidence of their role. We examined how so-called LC defects alter IOP-related mechanical insult to the LC neural tissues.

Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases.

Purpose: The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases.

Methods: Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging.

Role of radially aligned scleral collagen fibers in optic nerve head biomechanics.

Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head (ONH). Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal. Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure (IOP).

Peripapillary sclera architecture revisited: A tangential fiber model and its biomechanical implications.

Unlabelled: The collagen fiber architecture of the peripapillary sclera (PPS), which surrounds the scleral canal, is a critical factor in determining the mechanical response of the optic nerve head (ONH) to variations in intraocular pressure (IOP). Experimental and clinical evidence point to IOP-induced deformations within the scleral canal as important contributing factors of glaucomatous neural tissue damage and consequent vision loss. Hence, it is imperative to understand PPS architecture and biomechanics.

Seeing the Hidden Lamina: Effects of Exsanguination on the Optic Nerve Head.

Purpose: To introduce an experimental approach for direct comparison of the primate optic nerve head (ONH) before and after death by exsanguination.

Method: The ONHs of four eyes from three monkeys were imaged with spectral-domain optical coherence tomography (OCT) before and after exsanguination under controlled IOP. ONH structures, including the Bruch membrane (BM), BM opening, inner limiting membrane (ILM), and anterior lamina cribrosa (ALC) were delineated on 18 virtual radial sections per OCT scan.

Polarized light microscopy for 3-dimensional mapping of collagen fiber architecture in ocular tissues.

Collagen fibers play a central role in normal eye mechanics and pathology. In ocular tissues, collagen fibers exhibit a complex 3-dimensional (3D) fiber orientation, with both in-plane (IP) and out-of-plane (OP) orientations. Imaging techniques traditionally applied to the study of ocular tissues only quantify IP fiber orientation, providing little information on OP fiber orientation.

Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head Biomechanics.

Purpose: To model the sensitivity of the optic nerve head (ONH) biomechanical environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and central retinal artery blood pressure (BP).

Methods: We extended a previously published numerical model of the ONH to include 24 factors representing tissue anatomy and mechanical properties, all three pressures, and constraints on the optic nerve (CON). A total of 8340 models were studied to predict factor influences on 98 responses in a two-step process: a fractional factorial screening analysis to identify the 16 most influential factors, followed by a response surface methodology to predict factor effects in detail.

Lamina Cribrosa Pore Shape and Size as Predictors of Neural Tissue Mechanical Insult.

Purpose: The purpose of this study was to determine how the architecture of the lamina cribrosa (LC) microstructure, including the shape and size of the lamina pores, influences the IOP-induced deformation of the neural tissues within the LC pores using computational modeling.

Methods: We built seven specimen-specific finite element models of LC microstructure with distinct nonlinear anisotropic properties for LC beams and neural tissues based on histological sections from three sheep eyes. Changes in shape (aspect ratio and convexity) and size (area and perimeter length) due to IOP-induced hoop stress were calculated for 128 LC pores.

Formalin Fixation and Cryosectioning Cause Only Minimal Changes in Shape or Size of Ocular Tissues.

Advances in imaging have made it increasingly common to study soft tissues without first embedding them in plastic or paraffin and without using labels or stains. The process, however, usually still involves fixation and cryosectioning, which could deform the tissues. Our goal was to quantify the morphological changes of ocular tissues caused by formalin fixation and cryosectioning.

Microstructural Crimp of the Lamina Cribrosa and Peripapillary Sclera Collagen Fibers.

Purpose: Although collagen microstructural crimp is a major determinant of ocular biomechanics, no direct measurements of optic nerve head (ONH) crimp have been reported. Our goal was to characterize the crimp period of the lamina cribrosa (LC) and peripapillary sclera (PPS) at low and normal IOPs.

Methods: ONHs from 11 sheep eyes were fixed at 10-, 5-, or 0-mm Hg IOP and crimp periods measured manually from coronal cryosections imaged with polarized light microscopy (PLM).

Whole-globe biomechanics using high-field MRI.

The eye is a complex structure composed of several interconnected tissues acting together, across the whole globe, to resist deformation due to intraocular pressure (IOP). However, most work in the ocular biomechanics field only examines the response to IOP over smaller regions of the eye. We used high-field MRI to measure IOP induced ocular displacements and deformations over the whole globe.

Biomechanics of Cardiac Function.

The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function.

Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction.

Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42).

Myocardial Infarction Superimposed on Aging: MMP-9 Deletion Promotes M2 Macrophage Polarization.

In this study, we examined the combined effect of aging and myocardial infarction on left ventricular remodeling, focusing on matrix metalloproteinase (MMP)-9-dependent mechanisms. We enrolled 55 C57BL/6J wild type (WT) and 85 MMP-9 Null (Null) mice of both sexes at 11-36 months of age and evaluated their response at Day 7 post-myocardial infarction. Plasma MMP-9 levels positively linked to age in WT mice (r = .

Artery Remodeling Under Axial Twist in Three Days Organ Culture.

Arteries often endure axial twist due to body movement and surgical procedures, but how arteries remodel under axial twist remains unclear. The objective of this study was to investigate early stage arterial wall remodeling under axial twist. Porcine carotid arteries were twisted axially and maintained for three days in ex vivo organ culture systems while the pressure and flow remained the same as untwisted controls.

Cardiac aging is initiated by matrix metalloproteinase-9-mediated endothelial dysfunction.

Aging is linked to increased matrix metalloproteinase-9 (MMP-9) expression and extracellular matrix turnover, as well as a decline in function of the left ventricle (LV). Previously, we demonstrated that C57BL/6J wild-type (WT) mice > 18 mo of age show impaired diastolic function, which was attenuated by MMP-9 deletion. To evaluate mechanisms that initiate the development of cardiac dysfunction, we compared the LVs of 6-9- and 15-18-mo-old WT and MMP-9 null (Null) mice.

A model to determine the effect of collagen fiber alignment on heart function post myocardial infarction.

Background: Adverse remodeling of the left ventricle (LV) following myocardial infarction (MI) leads to heart failure. Recent studies have shown that scar anisotropy is a determinant of cardiac function post-MI, however it remains unclear how changes in extracellular matrix (ECM) organization and structure contribute to changes in LV function. The objective of this study is to develop a model to identify potential mechanisms by which collagen structure and organization affect LV function post-MI.

Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope.

Mathematical modeling of left ventricular dimensional changes in mice during aging.

Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results.

Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.

Rationale: Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored.

Objective: To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV).

Methods And Results: Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28((-/-)), n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI.

Bioreactor design for cornea tissue engineering: Material-cell interactions.

Several materials were evaluated for potential use in a bioreactor system for a tissue-engineered cornea. Two types of cytotoxicity tests were performed using human corneal stromal fibroblasts: a 24h cytotoxicity test based on the ASTM standard F813-01 and a 7 days growth inhibition test. It was determined that culture configuration, autoclaving and materials surface preparation were all important factors influencing cell viability.