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Neural-Glial-Vascular Interactions In Human Outer Retina, Deepayan Kar Jan 2023

Neural-Glial-Vascular Interactions In Human Outer Retina, Deepayan Kar

All ETDs from UAB

The outer retinal metabolic ecosystem is a complex interplay among photoreceptors, RPE and blood supply from the retinal and choroidal microcirculation. Breakdown of any component of this ecosystem has detrimental effects and can lead to cellular dysfunction. For example, in age-related macular degeneration a major cause of vision loss in older adults, breakdown of this metabolic unit has severe structural and functional implications. Thus, every feature and component of this ecosystem seems to be optimized to protect non-replicating, terminally differentiated cells from being damaged. Remarkably, much of the cellular and subcellular organization of this system is available for observation in …


Differential Recruitment Of Bone Marrow-Derived Cells Into The Injured Retina, Bright Asare-Bediako Jan 2023

Differential Recruitment Of Bone Marrow-Derived Cells Into The Injured Retina, Bright Asare-Bediako

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The hematopoietic system, which resides in the bone marrow in adults, maintains the constant turnover of blood cells in the circulatory system and supplies inflammatory/vascular reparative cells to the retina. Chronic metabolic diseases disrupt hematopoietic homeostasis, suppressing the generation of bone marrow-derived reparative cells in favor of pro-inflammatory cells. While much research has been done on development and disease-associated changes in hematopoiesis in the long bones and how mobilization to the retina is affected, the calvarium's hematopoiesis is underexplored. This dissertation investigated hematopoiesis in postnatal development and in disease, comparing calvarium hematopoiesis to that of long bones. The findings showed …


Towards Minimally Invasive Genetically Targeted Control Of Neural Activity Using X-Rays, Kelli Cannon Jan 2023

Towards Minimally Invasive Genetically Targeted Control Of Neural Activity Using X-Rays, Kelli Cannon

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X-genetics aims to replace visible light stimulation in optogenetics with X-radiation, offering improved bone penetration, minimal scattering, and enhanced targeting capabilities. This eliminates the need for surgical optic fiber implantation, reducing invasiveness and minimizing off-target effects. Discovering a receptor protein sensitive to X-rays or their byproducts is pivotal for advancing X-genetics.Two genetically encoded X-ray receptors (GEXRs) were investigated for X-genetics application: rhodopsin, historically associated with X-ray responses, and LITE-1, an unexpected candidate. Rhodopsin, when expressed in human embryonic kidney (HEK293) cells, demonstrated robust cAMP decreases upon visible light stimulation but remained unresponsive to moderate and high-dose X-rays, suggesting it may …


The Use Of Vesgen For Analysis Of Retinal Vasculature In Pulmonary Arterial Hypertension, Mariana Desiree Dupont Jan 2022

The Use Of Vesgen For Analysis Of Retinal Vasculature In Pulmonary Arterial Hypertension, Mariana Desiree Dupont

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Pulmonary artery hypertension is a chronic and progressive disease leading to right heart failure and, ultimately, death if untreated. The goal of the studies in this dissertation was to determine if fluorescein angiography (FA), and color fundus angiography (CF) imaging could be used to garner critical information about retinal changes in individuals with pulmonary artery hypertension (PAH). VESsel GENerational Analysis (VESGEN) is a noninvasive computer program that assigns branching generation to large and small vessels. VESGEN was utilized to investigate vascular alterations in FA, and CF imaging investigating disease progression in PAH. This dissertation demonstrated that PAH patients had aberrant …


Intrinsically-Photosensitive Retinal Ganglion Cells And Their Functional Roles, Kevin Q. Chang Jan 2022

Intrinsically-Photosensitive Retinal Ganglion Cells And Their Functional Roles, Kevin Q. Chang

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This project was conducted in Old World monkeys and focused on characterization of the intrinsically photosensitive retinal ganglion cells (ipRGCs) as they pertain to the pupillary light reflex, as well as on the neuroanatomical and electrophysiological characterization of the suprachiasmatic nucleus (SCN) of the hypothalamus as it pertains to circadian rhythms. A custom antibody was developed against the human melanopsin gene. We validated the antibody using western blot and immunohistochemistry. The functional role of ipRGCs in driving pupillary responses was investigated through immunotoxin-induced ablation in Rhesus macaques with the antibody conjugated to saporin. As hypothesized, the pupillary light reflex and …


Diagnostic Electrophysiology Of The Eye, Brooke Nicole Conner-Tsang Jan 2022

Diagnostic Electrophysiology Of The Eye, Brooke Nicole Conner-Tsang

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Aging and age-related changes in the brain are known to parallel functional and anatomical changes in the eye, especially in certain degenerative diseases. This study explores the potential of combining ERG, specifically the Pattern Electroretinogram (PERG), which has a black and white checkerboard pattern, and OCT tests to monitor retinal ganglion cell health. We compared ERG and OCT findings from ten normal females, ages ranging from 18 to 30 years old to ascertain if ganglion cell layer volume is a reliable indicator of ganglion cell function as measured by ERG. Our results from these healthy subjects will serve as prelude …


The Effect Of Training On Eye Movement While Learning To Use A Non-Foveal Retinal Locus, Jason Eugene Vice Jan 2022

The Effect Of Training On Eye Movement While Learning To Use A Non-Foveal Retinal Locus, Jason Eugene Vice

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Vision is our most far-reaching sense. It allows us to quickly detect information about the environment and enhances our ability to interact with the world around us. Accordingly, many neural areas are devoted to obtaining, processing, and interpreting visual information. When vision is impaired through normal aging or disease processes, the functional implications for a person can be quite significant. This is particularly true when a person is deprived of high acuity, central vision. Many people with bilateral central visual impairments learn to compensate for vision loss by adopting a viewing strategy that involves the use of the peripheral retina. …


Color Vision Testing With Readily Available Materials, Angel Perez Jan 2021

Color Vision Testing With Readily Available Materials, Angel Perez

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COLOR VISION TESTING WITH READILY AVAILABLE MATERIALS ANGEL PEREZ VISION SCIENCE ABSTRACT The perception of color is a process by which the brain discriminates different light wavelengths stimulating the cone photoreceptors in the retina of the eye. In humans each cone contains a photopigment making it most sensitive to either short (red), medium (green), or long (blue) wavelengths of light. However, when one of the cone pigments is defective or missing, color discrimination is reduced, resulting in color vision deficiency due to a deficient sex-linked chromosome in most cases. Color vision deficiency has the potential to impede many everyday activities, …


Patterns Of Medication Adherence In Glaucoma, Shervonne Poleon Jan 2021

Patterns Of Medication Adherence In Glaucoma, Shervonne Poleon

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Over 60 million persons globally are affected by primary open angle glaucoma (POAG)—an optic neuropathy characterized by distinctive patterns of vision loss. Glaucoma is a leading cause of irreversible blindness worldwide, and eye drops that delay vision loss are a common treatment modality. In glaucoma, the proportion of patients with good adherence to recommended therapy is reported to be low. High treatment cost, forgetfulness, and regimen complexity have been identified as key determinants of poor adherence. However, addressing these factors in the clinic is not as simple, as patient and provider values and priorities may differ. Without concordance, it can …


Glycoprotein 340 Expression In Dry Eye Disease And Ocular Surface Infection, Kwaku Antwi Osei Jan 2021

Glycoprotein 340 Expression In Dry Eye Disease And Ocular Surface Infection, Kwaku Antwi Osei

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Glycoprotein 340 (Gp340) is a 340-kDa multi-domain pattern recognition receptor (PRR) belonging to the scavenger receptor cysteine-rich superfamily of proteins. On the ocular surface, Gp340 is expressed in the tear film, lacrimal gland, cornea, and conjunctiva. By their nature, PRRs detect pathogen-associated molecular patterns (PAMPs) on microbial organisms and damage-associated molecular patterns (DAMPs) released from injured, stressed, necrotic, and apoptotic cells. This, in turn, induces the expression of nuclear factor-κB- and the interferon regulatory factor-dependent expression proinflammatory cytokines and chemokines, eliciting both innate and adaptive immune response activation. Thus, as a PRR, Gp340 has the potential to modulate microbial infection …


Role Of Trib3 In Progression And Pathogenesis Of Diabetic Retinopathy, Priyamvada Milind Pitale Jan 2020

Role Of Trib3 In Progression And Pathogenesis Of Diabetic Retinopathy, Priyamvada Milind Pitale

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Diabetic retinopathy (DR) is reported to be one of the leading causes of blindness in the United States by Center for Disease Prevention and Control. As the estimated prevalence of the disease will likely triple by 2020, the research in this area should focus on identifying novel targets and therapeutic approaches. One of the therapeutic approaches for DR is the reprograming of retinal metabolism to delay the progression of the disease. The unfolded protein response (UPR) is recognized as a cellular pathway activated in diabetic retina which interacts with key transcription factors to physiologically regulate glucose, lipid homeostasis, and angiogenic …


Characterization Of Intraocular Pressure Fluctuations, Intracranial Pressure And Translaminar Pressure Measured With Wireless Telemetry In Nonhuman Primates, Jessica Violet Jasien Jan 2020

Characterization Of Intraocular Pressure Fluctuations, Intracranial Pressure And Translaminar Pressure Measured With Wireless Telemetry In Nonhuman Primates, Jessica Violet Jasien

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Glaucoma is the second leading cause of blindness and third leading cause of visual impairment worldwide; 180 million people suffer from a glaucomatous visual disability. Glaucoma is an ocular neurodegenerative disease with several risk factors. The major identified risk factors of glaucoma are intraocular pressure (IOP), age, race, central cornea thickness, family history, and low diastolic blood pressure. The lowering of IOP is the only modifiable risk factor for the disease. However, we know little about the true character of IOP. Periodic IOP measurements are obtained every few months or at the discretion of the clinician during office hours and …


Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski Jan 2020

Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski

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Once thought to be no more than a vexing eye condition, ocular surface disease (OSD) is now being viewed as a differentiating factor between sight and no sight. In the setting of glaucoma, OSD can interfere with treatment success, potentially allowing the visually devastating pathology of glaucoma to plow onward with little restraint. Compounding the clinical challenge is the growing awareness that glaucoma-associated OSD appears to be iatrogenically induced by topical ophthalmic medications. Daily, topical instillation of preserved prostaglandin analogs (PGAs), the most common first-line treatment for glaucoma, has been linked to a variety of OSD subtypes, including meibomian gland …


Developing An Assessment Of Reading Impairment And Its Impact On Occupational Performance In Older Adults With Glaucoma In A Metropolitan Area Of The Southeastern Us: A Mixed Methods Approach, Robin Deacy Jan 2020

Developing An Assessment Of Reading Impairment And Its Impact On Occupational Performance In Older Adults With Glaucoma In A Metropolitan Area Of The Southeastern Us: A Mixed Methods Approach, Robin Deacy

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According to the United States Administration on Aging (AOA, 2014), the population of individuals over 65 will be 98 million by the year 2060, doubling its 2014 estimates. As our population ages, the prevalence of glaucoma increases. Vision loss resulting from glaucoma can limit participation in valued occupations including engagement in reading. It has long been thought that mobility issues and glare sensitivity were the main factors that characterized glaucoma. In the late 1990s and early 2000s researchers began to examine quality of life (QoL) in those with glaucoma. It was during these early QoL studies that the first reports …


Quality Of Life, Reading And Accommodation In Children With Low Vision, Dawn Kissner Decarlo Jan 2020

Quality Of Life, Reading And Accommodation In Children With Low Vision, Dawn Kissner Decarlo

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Childhood permanent, uncorrectable vision impairment (VI) is rare, yet it is a public health burden as the impairment lasts a lifetime. Vision impairment describes decreased vision that affects everyday activities. Acuity cut-points commonly used include 20/40, 20/60 or 20/70. Blindness often refers to legal blindness (best corrected visual acuity of 20/200 or worse or a visual field less than 20 degrees). Children with VI often have hereditary conditions such as albinism, optic atrophy and retinal degenerations and are different in many ways than adults with VI. The majority have conditions with onset at or near birth and as a result …


The Role Of Protein Synthesis Attenuation And Eif2-Alpha Phosphorylation In Retinal Degeneration, Christopher Ryan Starr Jan 2019

The Role Of Protein Synthesis Attenuation And Eif2-Alpha Phosphorylation In Retinal Degeneration, Christopher Ryan Starr

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Inherited retinal degeneration is a class of diseases in which there is no cure and very few treatment options available. An activated unfolded protein response has been detected in various animal models of retinal degenerative diseases. Several groups have found heightened activation of one pathway of the unfolded protein response in particular, the protein kinase R-like endoplasmic reticulum kinase signaling cascade, which converges on and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 to transiently halt protein synthesis and allow the cell to reestablish homeostasis. Although it is widely accepted that this signaling is inherently protective, hyperactivity or …


Role Of Developmental Protein, Nudc, In The Retina, Skyler Boehm Jan 2019

Role Of Developmental Protein, Nudc, In The Retina, Skyler Boehm

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Rod photoreceptors are the most prominent light sensitive cell in the retina of most mammals. The outer segments of photoreceptors contain the cellular machinery necessary for phototransduction to occur. The process of generating the phototransduction components occurs in the inner segment before being trafficked to the outer segment. These processes are highly regulated and require many different trafficking proteins and chaperones. The developmental protein nuclear distribution gene C (nudC) was found to be present in the photoreceptor, but its function is yet to be determined. Here we confirm that nudC is present in the retina and necessary in the photoreceptors. …


Integration Of Cone Photoreceptor Signals In Macaque Lgn Neurons, Paul B. Brown Jan 2019

Integration Of Cone Photoreceptor Signals In Macaque Lgn Neurons, Paul B. Brown

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Despite advances in the understanding of the primate visual system, much is yet to be learned about the way light signals sum to create our perception of the world. This is especially true at the simplest level of visual processing—the summation of two individual cone photoreceptor signals. How such signals combine to create visual perception has not been assessed in vivo. We used an adaptive optics scanning laser ophthalmoscope (AOSLO) to deliver binarized noise movies to identified groups of cones within the receptive fields of neurons in the macaque lateral geniculate nucleus (LGN). Recordings of neural action potentials within the …


A Microfocal Effect In Photoreceptor Light Capture, Vasantha Kumari Kanukuntla Jan 2019

A Microfocal Effect In Photoreceptor Light Capture, Vasantha Kumari Kanukuntla

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In human eyes, accomodation brings light rays into focus on the retina in order to achieve a clear images. The plane of best focus within the depth of the retina is thought to be within the photoreceptor layer, but pinpointing the exact focal position axially has not been determined. With help of adaptive optics aberration correction and its ability to have microscopic control of a retinal stimulus, we explored how sensitive human subjects are to defocus on the micron scale. We found that focal position can be reliably judged within 0.02 D, which is equivalent to about 6 microns in …


The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff Jan 2019

The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff

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Every night, during sleep, the tears of the closed eye become significantly more inflammatory, with a notable influx of neutrophils. Preliminary studies suggested that these neutrophils were significantly different than blood-isolated neutrophils, with an increased concentration, upregulated surface expression of inflammatory membrane receptors, but inability to respond to inflammatory stimuli. The purpose of this dissertation was to better understand the contribution of this neutrophil population to ocular surface homeostasis and dry eye disease. Chapter One presents an introduction to the tear film and ocular surface, along with an introduction to dry eye disease and neutrophil biology. Chapter One also discusses …


Intraocular Pressure Dynamics, Daniel Coleman Turner Jan 2019

Intraocular Pressure Dynamics, Daniel Coleman Turner

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While cataracts (the leading cause of blindness worldwide) can be reversed surgical-ly, glaucoma is the leading cause of irreversible blindness, affecting over 70 million people worldwide [1]. Elevated intraocular pressure (IOP) and age are the primary risk factors for glaucoma [2] and lowering IOP is the only proven treatment for the disease [3]. IOP and its fluctuations affect nearly every aspect of ocular physiology and homeo-stasis, as well as playing a dominant role in glaucoma pathophysiology, yet very little is known about IOP due to the current clinical standard of measuring mean IOP during infre-quent clinic visits. We use a …


Connecting Cilium Proteins Bbs5 And Mks6 And Their Roles In Retinal Degeneration, Katie Leigh Bales Jan 2018

Connecting Cilium Proteins Bbs5 And Mks6 And Their Roles In Retinal Degeneration, Katie Leigh Bales

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The primary cilium is an evolutionary conserved structure with numerous motility and sensory-related functions, dynamically concentrating signaling molecules to developmental, homeostatic and sensory pathways. Rod and cone photoreceptor cells are highly modified primary cilia, which reside in the back of the eye within the neural retina and are responsible for dim light sensitivity and visual acuity/ color vision, respectfully. These cells require massive protein production and proper protein trafficking on a daily basis. The major protein complexes that govern protein trafficking within photoreceptors form the connecting cilium, are the transition zone which serves as a gatekeeper, regulating protein trafficking into …


Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz Jan 2018

Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz

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Mucins on the ocular surface are found in the tear film and are attached to corneal and conjunctival epithelial cells on the eye. The bulbar conjunctiva of the ocular surface can be divided into four anatomical regions: temporal, superior, nasal, and inferior. The palpebral conjunctiva is the epithelial layer of the inner surfaces of the upper and lower eyelids. In the tears, mucins provide lubrication of the ocular surface through formation of a hydrophilic gel. The primary mucin in the tear film is MUC5AC which is secreted by goblet cells that are located in varying densities within the bulbar conjunctiva. …


Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks Jan 2018

Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks

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GARP2, found exclusively in retinal rod photoreceptors, has been proposed to function as a structural protein, a calcium binding protein, and a modulator of the phosphodiesterase regulating visual phototransduction cascade kinetics. GARP2 is a splice variant of the Cngb1 gene which also encodes the β-subunit of the phototransduction cyclic nucleotide-gated cation channel and another glutamic acid-rich protein, GARP1. Mutations of the β-subunit and, recently discovered regions shared with the GARP en-coding regions of Cngb1cause retinitis pigmentosa (RP), while overexpression of GARP2 in the absence of the β-subunit accelerates the observed Cngb1-mediated retinal degeneration in mouse β-subunit knockout disease models. In …


Lipid Biomarkers And Pathway Identification For Contact Lens Related Discomfort, Shyam Panthi Jan 2017

Lipid Biomarkers And Pathway Identification For Contact Lens Related Discomfort, Shyam Panthi

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The purpose of this investigation was to identify possible lipid biomarkers that are associated with contact lens related discomfort and determine whether inflammation as a result of lipid peroxidation or enzymatic arachidonic acid metabolism is associated with such discomfort. Ten microliters of tears were collected from each eye of fifteen subjects (11 non-contact lens wearers, 2 contact lens wearers with discomfort and 2 contact lens wearers without discomfort) and assayed using various chemical extraction methods and mass spectrometry based analytical approaches. This was done to determine whether lipid mediators of inflammation could be identified in low volume (10 l) of …


A Comparison Between Number And Letter Acuities Among Patients, Sarah Berry Jan 2017

A Comparison Between Number And Letter Acuities Among Patients, Sarah Berry

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ABSTRACT Purpose: Previous studies have shown that there is an association between visual acuity and Alzheimers’ disease. Untreated visual problems may contribute to cognitive impairment and more progressive cognitive decline. This study investigates the association of chart design, specifically comparing charts using letters versus numbers, to accuracy and repeatability among patients with dementia. Methods: 23 English-speaking subjects diagnosed with moderate to advanced levels of dementia were recruited from two local Birmingham nursing homes. Visual acuities were measured in a randomly selected eye and timed from six different charts: Back-illuminated ETDRS chart with letters, Back-illuminated ETDRS chart with numbers, HOTV cards …


Oxygen Permeability (Dk) Of Silicone-Hydrogel Materials: Relationship With Water, Silicon, And Fluorine Contents, Terin E. Dupre Jan 2017

Oxygen Permeability (Dk) Of Silicone-Hydrogel Materials: Relationship With Water, Silicon, And Fluorine Contents, Terin E. Dupre

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To more precisely determine the fundamental relationships between oxygen permeability (Dk), water content (WC), silicon (Si) content, and fluorine (F) content of clinically prescribed silicone-hydrogel (SiHy) materials, identical methodologies for 16 commercially available brands of SiHy materials were performed. Dk and WC were determined according to the ANSI and ISO standards and, with Si and F contents, on the same lot numbers of samples across a common range of available refractive powers. A negative linear relationship was found between Si content and water content. Lotrafilcon A, Lotrafilcon B, and the bulk polymer of Delefilcon A initially deviated from this relationship. …


The Eye As A Window To The Alzheimer’S Disease Brain, Fred Souza Jan 2017

The Eye As A Window To The Alzheimer’S Disease Brain, Fred Souza

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Alzheimer’s disease (AD) is a debilitating, and the most prevalent, type of dementia that is manifested by cognitive deficits, anomalous protein metabolism, cell loss, and pathological alterations in several neurotransmitter systems, particularly the cholinergic and glutamatergic systems. Moreover, AD is associated with visual deficits that have been reported to occur even in the early stages of the disease and may precede conspicuous cognitive impairment. To date, the underlying causes of the visual deficits and whether they stem from retinal or cortical abnormalities remain poorly understood. The following studies aimed at establishing whether the pathological changes observed in the cerebrum are …


Histopathology And Image Validation Of Outer Retinal Tubulations In Age-Related Macular Degeneration, Katie M. Litts Jan 2016

Histopathology And Image Validation Of Outer Retinal Tubulations In Age-Related Macular Degeneration, Katie M. Litts

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High-resolution imaging of the retina using spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) is revealing new information about photoreceptor degeneration in age-related macular degeneration (AMD) and other diseases impacting rod and cone photoreceptors. By SD-OCT, the hyperreflective outer retinal bands are visible due to the precise vertical compartmentalization and horizontal alignment of outer retinal cells and tissues (Müller cells, photoreceptors, RPE, and Bruch’s membrane). Validating these bands with normal eyes is difficult because the outer retina is very delicate making accurate histology requiring attached retina and vertically aligned photoreceptors challenging. Conversely, the bands are …


Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow Jan 2016

Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow

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Purpose: The aim of this study was to adapt conjunctival impression cytology (CIC) and RNA isolation to genetic analysis of the conjunctival surface of keratoconus (KC) patients with (AKC) and without atopic disease (AD) and with normal contact lens wearers (NCL). If RNA quantity and quality was sufficient, full transcriptome analysis would be conducted using RNA-Seq, rather than the more limited microarray approach. Methods: CIC samples were the ocular surface of 30 participants from four groups: 1) KC, 2) AKC, 3) AD, and 4) NCL. Several extraction and purification methods were investigated, including density gradient centrifugation, precipitation, conventional pelleting, and …