Nicole Gullatt_Project Engages Presentation (Spring Semester Presentation)

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Modeling the Effects of Bruchs Membrane Opening Shape on the Biomechanics of the Rat Model of Glaucoma

Nicole GullattDr. C. R. Ethiers LabMentor: Stephen SchwanerMay 16, 2016

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Glaucoma Overview: What is it?Glaucoma is a group of eye diseases involving optic nerve damage and usually involving an increase of intra-ocular pressure (IOP)Elevated IOP causes increased stressed and strain in the optic nerve head (ONH) tissues resulting in retinal ganglion cell death and preventing the transmission of visual information to the brainTreatment for glaucoma is centered around preventing further loss because eye damage and vision loss that has already occurred is irreversible Medications and surgical treatments for glaucoma focus on lowering a patients IOP, but are not always effective

Why the rat model is studied for glaucoma research:It is unethical to conduct scientific experiments on humans.Rodent models are necessary for high throughput studies due to their low cost and ease of caring forRats present similar optic nerve head damage patterns to humans after experiencing elevated IOP

Glaucoma is complex and often times misunderstood optic neuropathy of unknown etiology. Etiology: set of causes, or manner of causation of a disease or condition.Women are three times more likely than men to develop acute angle closure glaucoma due to their shallower anterior chambers.2

Biomechanics of the Optic Nerve Head (ONH)The complex pathophysiology of glaucoma is driven by biomechanicsElevated IOP leads to stress and strain in the ONH.Stress: force per unit areaStrain: ratio of an objects deformation to its original shapeIOP related stress and strain can affect the delivery of nutrients to the RGC axons and axonal transport, and the activation of astrocytes in the ONHDistribution of stress and strain in the ONH is complicated

Stress: the amount of force applied to an object per surface areaStrain: ratio of deformity to the original shape of an object

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My Research Focus: Computer Modeling1. Use design program Multiview to obtain 3-D point clouds of tissue geometry2. Create 2-D circular plane (radius: 1 mm) with BMO shape in Rhino3. Import 2-D plane into Abaqus and assign material properties:Youngs Modulus: 3 MPaPoissons Ratio: 0.49

Multiview Delineations of Histology Slide MR4-ODBMO shapes acquired in Multiview

Circular Plane Rhino

Circular Plane with material properties in Abaqus

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My Research Focus: Computer Modeling4. Create polar coordinate system for 2-D Plane Section in Abaqus Biaxial Displacement: 10 m in radial directionBoundary Condition: constrained in z direction5. Mesh 2-D Plane in Abaqus Meshing breaks geometrical figures into elements6. Simulate stress and strain levels at locations in the eye using Abaqus

2-D Plane with loads and boundary conditions in AbaqusMeshed 2-D Plane with elements in Abaqus

Solve the model in Abaqus to simulate strain levels around BMO

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Results

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Conclusion Differences in 95th percentile strain of up to 30% were predicted between models. This suggests that BMO shape could be an important factor in the rat model of glaucoma and that a more irregular BMO shape could potentially increase susceptibility to IOP-related damage in glaucoma.

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Summer Research: Saponin Treatments for Pig TM Cells The trabecular meshwork is an area of tissue in the eye located around the cornea, responsible for removing the aqueous humor from the eye.Project Goal: Find the appropriate concentration of saponin to kill approximately 80% of pig trabecula meshwork cells to develop a glaucoma model.

Acknowledgments

I wish to acknowledge Dr. C. R. Ethier, Stephen Schwaner, Eric Snider, and members of the Either Lab for their assistance with this research. Thank You!

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Pathophysiology of Glaucomatous DamageThe pathophysiology of glaucoma involves multiple cell and tissue types in the optic nerve head including:Connective Tissues Neural CellsCells that interact with neural and connective tissuesGlaucomatous damage is caused by a complex set of factors including:IschemiaInflammationAstrocyte functionThese factors are intermediate steps between elevated IOP and retinal ganglion cell death (RGC)

Pathophysiology: disordered physiological processes associated with disease or injuryConnective Tissues: scleral tissues and lamina cribrosaNeural Tissues: retinal ganglion cellsOther Cells: astrocytes, glial cells, and endothelial cellsIschemia: an inadequate blood supply to an organ or part of the bodyAstrocyte Biology = Astrocyte Structure & Function

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My Research Focus: Bruchs MembraneBruchs MembraneBruchs membrane is located between retinal pigmented epithelium and the choroidBruchs membrane is an elastin and collagen rich extra-cellular matrix Partially regulates the exchange of biomolecules, nutrients, and oxygenUltimate GoalDetermine if Bruchs membrane opening shape affects ONH biomechanics by creating 3-D models of the rat ONH

Bruchs Membrane

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Computer ModelingDelineations in Mulitiview of various tissues within the ONH. This program is used to:Get the geometry of the ONH tissuesDevelop a point cloud

Multiview Delineations of Histology Slide MR4-ODBruchs Membrane

Bruchs membrane opening shapes acquired in Multiview

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Slide about meshing, applying loads, and getting stresses and strains

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ConclusionPicture of solved modelRelate it back to the complex pathophysiology

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Title and Content Layout with Chart

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Two Content Layout with TableFirst bullet point hereSecond bullet point hereThird bullet point hereGroup 1Group 2Class 18295Class 27688Class 38490

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Title and Content Layout with SmartArt

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