Browsing by Author "Ophthalmology, School of Medicine"
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Item A narrative review on the association of high intraocular pressure and glaucoma in patients with retinal vein occlusion(AME Publishing Company, 2022) Jabbehdari, Sayena; Yazdanpanah, Ghasem; Cantor, Louis B.; Hajrasouliha, Amir Reza; Ophthalmology, School of MedicineBackground and objective: Retinal vein occlusion (RVO) is a major cause of vision loss and elevated intraocular pressure (IOP), high ocular perfusion pressure, and glaucoma are known ophthalmic risk factors for RVO. The aim of this paper is to provide the update on the association and management of high IOP/glaucoma and RVO. Methods: A literature review was performed in PubMed and Medline until May 2022 utilizing specific keywords and cross-matched reference lists. Key content and findings: The association of RVO with high IOP/glaucoma may be attributed to retinal ganglion cell loss due to retinal ischemia in high IOP and glaucoma. As new modalities showed, decreased optic disc perfusion, reduced density of blood vessels in the optic nerve head of glaucoma patients, changes in the peripapillary microvascular parameters, and decreased retinal nerve fiber layer (RNFL) thickness of the optic nerve head of eyes with RVO suggest a common pathway between RVO and glaucoma. Literature suggests the close follow up for glaucoma development among patients with non-arteriovenous (AV) crossing (optic cup or optic nerve sited) RVO in fellow eye and management of elevated IOP among RVO cases treated with anti-vascular endothelial growth factor (VEGF) antibodies/corticosteroids and those with preexisting primary open angle glaucoma (POAG). Conclusions: Determining potential patient responses to treatment and considering therapeutic options are challenging among patients with RVO and glaucoma. However, IOP lowering managements in preventing IOP spikes in patients with preexisting glaucoma and early treatment of macular edema in eyes with RVO is recommended.Item A Novel Technique Identifies Valve-Like Pathways Entering and Exiting Schlemm's Canal in Macaca nemestrina Primates With Similarities to Human Pathways(Frontiers Media, 2022-07-04) Martin, Elizabeth A.; Johnstone, Murray A.; Ophthalmology, School of MedicinePurpose: The aim of the study was 1) to describe a novel combination of techniques that permit immunohistochemistry imaging of Schlemm's canal inlet (SIV) and outlet (SOV) valve-like structures, 2) to identify tissue-level SIV adhesive relationships linking the trabecular meshwork (TM) to hinged collagen leaflets at the Schlemm's canal (SC) external wall, and 3) to determine whether the SIV lumen wall's adhesive vascular markers are similar to those of the SC inner wall endothelium. Materials and Methods: Anterior segments of 16 M. nemestrina primates underwent immunohistochemistry (IHC) labeling. We perfused fluorescent microspheres into 12 of the eyes. Limbal tissues were divided into quadrants, viscoelastic introduced into SC, tissues fixed, immunohistochemistry performed, radial segments cut, tissues clarified, and confocal microscopy performed. Finally, we generated ImageJ 3D projections encompassing the TM, SC, and distal pathways. Results: IHC imaging identified 3D relationships between SIV, collector channel ostia, collector channels (CC), SOV, and intrascleral channels. Imaging depth increased 176.9%, following clarification (p < 0.0001). Imaging demonstrated CD31, collagen type 1 and 4 in the walls of the SIV lumen and more distal pathways. In eight eyes, 384 segments were examined, 447 SIV identified, and 15.4% contained microspheres. Conclusion: Our technique's imaging depth permitted the identification of SIV linkage between the TM and SOV. We found comparable cell-cell adhesion molecules (CD31) and basement membrane components in the SC inner wall and SIV lumen walls. Recent OCT studies have suggested that SIV tensional relationships may control CC entrance dimensions that regulate distal resistance. Cellular adhesive properties sustain SIV tensional relationships. These SIV cell-cell and cell-basement membrane properties warrant further study because abnormalities could be a factor in the IOP elevation of glaucoma.Item Advanced glycation end (AGE) product modification of laminin downregulates Kir4.1 in retinal Müller cells(PLOS, 2018-02-23) Thompson, Kayla; Chen, Jonathan; Luo, Qianyi; Xiao, Yucheng; Cummins, Theodore R.; Bhatwadekar, Ashay D.; Ophthalmology, School of MedicineDiabetic retinopathy (DR) is a major cause of adult blindness. Retinal Müller cells maintain water homeostasis and potassium concentration via inwardly rectifying Kir4.1 channels. Accumulation of advanced glycation end products (AGEs) is a major pathologic event in DR. While diabetes leads to a decrease in the Kir4.1 channels, it remains unknown whether AGEs-linked to the basement membrane (BM) affect normal Kir4.1 channels. For this study, we hypothesized that AGE-modification of laminin is detrimental to Kir4.1 channels, therefore, disrupting Müller cell function. The AGE-modified laminin-coated substrates were prepared by incubating Petri-dishes with laminin and methylglyoxal for seven days. The rat Müller cells (rMC-1) were propagated on AGE-modified laminin, and Kir4.1 expression and function were evaluated. Quantification of AGEs using ELISA revealed a dose-dependent increase in methylglyoxal-hydro-imidazolone adducts. The rMC-1 propagated on AGE-modified laminin demonstrated a decrease in Kir4.1 levels in immunofluorescence and western blot studies and a decrease in the Kir4.1 channel function. Kir4.1 decrease on AGE-modified laminin resulted in a disorganization of an actin cytoskeleton and disruption of α-dystroglycan-syntrophin-dystrophin complexes. Our studies suggest that AGE-modification of laminin is detrimental to Kir4.1 channels. By studying the role of AGEs in Kir4.1 channels we have identified a novel mechanism of Müller cell dysfunction and its subsequent involvement in DR.Item Advancing Nerve Regeneration: Translational Perspectives of Tacrolimus (FK506)(MDPI, 2023-08-14) Daeschler, Simeon C.; Feinberg, Konstantin; Harhaus, Leila; Kneser, Ulrich; Gordon, Tessa; Borschel, Gregory H.; Ophthalmology, School of MedicinePeripheral nerve injuries have far-reaching implications for individuals and society, leading to functional impairments, prolonged rehabilitation, and substantial socioeconomic burdens. Tacrolimus, a potent immunosuppressive drug known for its neuroregenerative properties, has emerged in experimental studies as a promising candidate to accelerate nerve fiber regeneration. This review investigates the therapeutic potential of tacrolimus by exploring the postulated mechanisms of action in relation to biological barriers to nerve injury recovery. By mapping both the preclinical and clinical evidence, the benefits and drawbacks of systemic tacrolimus administration and novel delivery systems for localized tacrolimus delivery after nerve injury are elucidated. Through synthesizing the current evidence, identifying practical barriers for clinical translation, and discussing potential strategies to overcome the translational gap, this review provides insights into the translational perspectives of tacrolimus as an adjunct therapy for nerve regeneration.Item Age and sex affect TGFβ2-induced ocular hypertension in C57BL/6J mice(Elsevier, 2022) Sugali, Chenna Kesavulu; Rayana, Naga Pradeep; Dai, Jiannong; Peng, Michael; Mao, Weiming; Ophthalmology, School of MedicineGlaucoma is a leading cause of blindness worldwide. The loss of vision in glaucoma patients is due to optic nerve damage. The most important risk factor of glaucoma is elevated intraocular pressure (IOP) which is due to glaucomatous changes in the trabecular meshwork. Animal models, especially mouse models for ocular hypertension (OHT), are important for studying glaucoma. Published studies showed that 2.5X107 PFU adenoviral vectors expressing the biologically active form of human TGFβ2 elevate IOP in female C57BL/6J mice when they are intravitreally delivered. In this study, we found that 2.5X107 PFU adenoviral TGFβ2 vector did not elevate IOP in 3- or 5-month old male C57BL/6J mice. In contrast, 5X107 PFU of the same viral vectors elevated IOP in both 3- and 5-month old male C57BL/6J mice. Also, 5-month old mice showed earlier OHT and higher IOP compared to 3-month old mice. In summary, our data showed that age and sex play roles in adenoviral vector-mediated TGFβ2-induced OHT in C57BL/6J mice.Item Alzheimer's disease and primary open‐angle glaucoma associated with vascular health in patients of African descent(Wiley, 2018-12) Hutchins, Katherine; Harris, Alon; Thomas, Joseph; Alkhairy, Sameerah; Vercellin, Alice Chandra Verticchio; Shah, Aaditya; Siesky, Brent; Ophthalmology, School of MedicineItem Amblyopia Preferred Practice Pattern(Elsevier, 2023) Cruz, Oscar A.; Repka, Michael X.; Hercinovic, Amra; Cotter, Susan A.; Lambert, Scott R.; Hutchinson, Amy K.; Sprunger, Derek T.; Morse, Christie L.; Wallace, David K.; American Academy of Ophthalmology Preferred Practice Pattern Pediatric Ophthalmology/Strabismus Panel; Ophthalmology, School of MedicineItem An ex vivo model of human corneal rim perfusion organ culture(Elsevier, 2022) Peng, Michael; Margetts, Tyler J.; Sugali, Chenna Kesavulu; Rayana, Naga Pradeep; Dai, Jiannong; Sharma, Tasneem P.; Raghunathan, Vijay Krishna; Mao, Weiming; Ophthalmology, School of MedicineThe human anterior segment perfusion culture model is a valuable tool for studying the trabecular meshwork (TM) and aqueous humor outflow in glaucoma. The traditional model relies on whole eye globes resulting in high cost and limited availability. Here, we developed a glue-based method which enabled us to use human corneal rims for perfusion culture experiments. Human corneal rim perfusion culture plates were 3D printed. Human corneal rims containing intact TM were attached and sealed to the plate using low viscosity and high viscosity glues, respectively. The human corneal rims were perfused using the constant flow mode, and the pressure changes were recorded using a computerized system. Outflow facility, TM stiffness, and TM morphology were evaluated. When perfused at rates from 1.2 to 3.6 μl/min, the outflow facility was 0.359 ± 0.216 μl/min/mmHg among 10 human corneal rims. The stiffness of the TM in naïve human corneal rim was similar to that of perfusion cultured human corneal rim. Also, the stiffness of TM of corneal rims perfused with dexamethasone was significantly higher than the control. Human corneal rims with glue contamination in the TM could be differentiated by high baseline intraocular pressure as well as high TM stiffness. Histology studies showed that the TM tissues perfused with plain medium appeared normal. We believed that our glued-based method is a useful tool and low-cost alternative to the traditional anterior segment perfusion culture model.Item An improved method for murine laser-induced choroidal neovascularization lesion quantification from optical coherence tomography images(Elsevier, 2022-08-02) Jensen, Nathan R.; Lambert-Cheatham, Nathan; Hartman, Gabriella D.; Muniyandi, Anbukkarasi; Park, Bomina; Sishtla, Kamakshi; Corson, Timothy W.; Ophthalmology, School of MedicineLaser-induced choroidal neovascularization (L-CNV) in murine models is a standard method for assessing therapies, genetics, and mechanisms relevant to the blinding eye disease neovascular or "wet" age-related macular degeneration. The ex vivo evaluation of these lesions involves confocal microscopy analysis. In vivo evaluation via optical coherence tomography (OCT) has previously been established and allows longitudinal assessment of lesion development. However, to produce robust data, evaluation of many lesions may be required, which can be a slow, arduous process. A prior, manual method for quantifying these lesions as ellipsoids from orthogonal OCT images was effective but time consuming. We therefore developed an OCT lesion quantification that is simplified, streamlined, and less time-consuming.Item Analysis of Lipid Contents in Human Trabecular Meshwork Cells by Multiple Reaction Monitoring (MRM) Profiling Lipidomics(Springer, 2023) Wang, Ting; Pattabiraman, Padmanabhan Paranji; Ophthalmology, School of MedicineLipids are among the major constituents of cells and play many important cellular functions. Lipid levels in the trabecular meshwork (TM) aqueous humor outflow pathway play an important role in the maintenance of aqueous humor drainage and intraocular pressure (IOP) homeostasis. Therefore, it is important to characterize the changes in the lipid contents in the aqueous humor outflow pathway tissues to better understand their functional significance in the maintenance of IOP. The multiple reaction monitoring (MRM)-based profiling aids in the analysis of the metabolome as a collection of functional groups and is utilized as an exploratory metabolomics and lipidomics approach. The MRM-based profiling utilizes tandem mass spectrometry experiments carried out on a commercial triple quadrupole mass spectrometer with three aligned quadrupole mass filters (Q1, Q2, and Q3). This screening methodology can be utilized for targeted lipidomics screening. This chapter focuses on the methodology for isolation and culturing of the TM cells, lipid extraction, and the MRM-based lipidomics approach with data analysis.