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You searched for subject:(conventional outflow). Showing records 1 – 3 of 3 total matches.

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1. O'CALLAGHAN, JEFFREY. A novel gene-based therapy for galaucoma:from discovery to preclinical development.

Degree: School of Genetics & Microbiology. Discipline of Genetics, 2018, Trinity College Dublin

Introduction: Glaucoma is a multifactorial condition that will often result in complete bilateral blindness if untreated. Elevated intraocular pressure (IOP) is both a major risk factor and indicator of disease. IOP is maintained by the balance between production of aqueous humour (AH) by the ciliary processes and hydrodynamic resistance to its outflow through the conventional outflow pathway comprising the trabecular meshwork (TM) and Schlemm?s canal (SC). Since a significant proportion of glaucoma patients develop resistance to pressure-reducing topical formulations, there remains a significant unmet clinical need for medications acting upon the conventional pathway. Matrix metalloproteinases (MMPs) contribute to conventional aqueous outflow homeostasis through their capacity to remodel extracellular matrices, which has a direct impact on aqueous outflow resistance and IOP. In this regard, an AAV-mediated gene therapy targeting the conventional outflow pathway using an MMP secreted from the corneal endothelium into the anterior chamber, increasing AH outflow and reducing IOP has been developed in mice following intracameral inoculation. Methods: TEER and flux assays were performed on SC and TM monolayers to observe the effect of multiple cytokines on permeability. RT-PCR and western blot was used to identify levels of MMP expression in response to such cytokines. Healthy and glaucomatous AH were assayed by ELISA and FRET to quantify the concentration and activity of MMP-3. Recombinant MMP-3 was further assayed for its effect on monolayer permeability. An AAV-2/9 containing a CMV or tetracycline promoter-driven MMP-3 gene was intracamerally injected into wild type mice and into mice modelling glaucoma induced by dexamethasone or by expression of a dominant-acting human myocilin transgene. Immunohistochemistry was performed on anterior segment cryosections to assess MMP-3 expression in the anterior chamber and immunocytochemistry/western blot were performed to ascertain substrate cleavage. IOP and outflow facility readings were performed on injected murine eyes to ascertain the effect of virally delivered MMP-3 on AH flow dynamics. Transmission electron microscopy was used to observe the physical effect of treatment on the outflow pathway. Results: MMP-3 was identified as an attractive target for secretion into the anterior chamber. Decreased MMP-3 activity was observed in human glaucomatous AH compared to age-matched normotensive control AH. Treatment with glaucomatous AH resulted in significantly increased transendothelial resistance of SC endothelial and TM cell monolayers, and reduced monolayer permeability when compared to control AH or supplemented treatment with exogenous MMP-3. Intracameral inoculation of AAV-2/9 containing a CMV-driven MMP-3 gene (AAV-MMP-3) into wild type mice resulted in efficient transduction of corneal endothelium and an increase in aqueous concentration and activity of MMP-3. Most notably, AAV-mediated expression of MMP-3 increased outflow facility and decreased IOP. Controlled… Advisors/Committee Members: Humphries, Peter.

Subjects/Keywords: MMP3; Matrix metaloproteinase; Gene therapy; Adeno associated virus; corneal endothelium; conventional outflow; IOP; Glaucoma; outflow facility

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APA (6th Edition):

O'CALLAGHAN, J. (2018). A novel gene-based therapy for galaucoma:from discovery to preclinical development. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/84993

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

O'CALLAGHAN, JEFFREY. “A novel gene-based therapy for galaucoma:from discovery to preclinical development.” 2018. Thesis, Trinity College Dublin. Accessed November 21, 2019. http://hdl.handle.net/2262/84993.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

O'CALLAGHAN, JEFFREY. “A novel gene-based therapy for galaucoma:from discovery to preclinical development.” 2018. Web. 21 Nov 2019.

Vancouver:

O'CALLAGHAN J. A novel gene-based therapy for galaucoma:from discovery to preclinical development. [Internet] [Thesis]. Trinity College Dublin; 2018. [cited 2019 Nov 21]. Available from: http://hdl.handle.net/2262/84993.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

O'CALLAGHAN J. A novel gene-based therapy for galaucoma:from discovery to preclinical development. [Thesis]. Trinity College Dublin; 2018. Available from: http://hdl.handle.net/2262/84993

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of South Florida

2. Ficarrotta, Kayla R. Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats.

Degree: 2018, University of South Florida

Glaucoma affects tens of millions of people and is the leading cause of irreversible blindness worldwide. Virtually all current glaucoma therapies target elevated intraocular pressure (IOP); however, the contribution of intracranial pressure (ICP) to glaucoma has recently garnered interest. Strain at the optic nerve head is now known to depend on the translaminar pressure difference (TLPD), which is the difference between IOP and ICP, rather than IOP alone. A better understanding of how IOP and ICP relate to glaucoma development and progression is essential for developing improved therapies and diagnostic tests. Glaucoma is commonly modeled in rats, yet aqueous humor dynamics are not well-documented in healthy nor diseased rat eyes. Moreover, because rats do not develop glaucoma spontaneously, it is essential to develop low-cost, reliable, and relevant models of glaucomatous pathology in the animal. The purpose of this dissertation work is to achieve the following goals: i) quantitatively assess aqueous humor dynamics in healthy, living rat eyes, ii) develop an ideal model of experimental glaucoma in rats, iii) quantitatively characterize aqueous humor dynamics throughout experimental glaucoma in living rats, and iv) investigate the effects of ICP manipulations on aqueous humor dynamics in living rats. Chapter 2 reports physiological parameters of aqueous humor dynamics for the first time in the eyes of living, healthy Brown-Norway rats, and presents a novel perfusion technique for efficiently and accurately estimating these parameters. Chapter 3 introduces the constant-pressure perfusion model of experimental glaucoma: a powerful new model which overcomes several limitations of existing techniques. The constant-pressure perfusion model induces IOP elevations which are prescribable and easily manipulated, does not directly target the trabecular meshwork or its vasculature, and offers continuous records of IOP rather than requiring regular animal handling and tonometry. Chapter 3 characterizes IOP-induced optic neuropathies in rats and demonstrates their resemblance to human glaucoma. Chapter 4 evaluates whether the constant-pressure perfusion model affects ocular physiology, specifically showing that resting IOP and conventional outflow facility are not permanently nor significantly altered in the model. Chapter 5 examines the effect of ICP manipulations on aqueous outflow physiology in living rats, and reports for the first time a graded effect of intracranial hypertension on conventional outflow facility. Evidence for a neural feedback mechanism that may serve to regulate the TLPD is also presented. Chapter 6 summarizes the results of this dissertation, provides recommendations for future work, and gives closing remarks. These collective projects provide insight into IOP regulation in both healthy and diseased rat eyes, advancing our understanding of glaucomatous development and damage in rats. A novel model of experimental glaucoma and several perfusion systems have been developed which are distinctly tailored for…

Subjects/Keywords: Conventional Outflow Facility; Glaucoma; Intracranial Pressure; Intraocular Pressure; Ocular Hypertension; Biomedical Engineering and Bioengineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ficarrotta, K. R. (2018). Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/7503

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Ficarrotta, Kayla R. “Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats.” 2018. Thesis, University of South Florida. Accessed November 21, 2019. https://scholarcommons.usf.edu/etd/7503.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Ficarrotta, Kayla R. “Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats.” 2018. Web. 21 Nov 2019.

Vancouver:

Ficarrotta KR. Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats. [Internet] [Thesis]. University of South Florida; 2018. [cited 2019 Nov 21]. Available from: https://scholarcommons.usf.edu/etd/7503.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ficarrotta KR. Aqueous Humor Dynamics and the Constant-Pressure Perfusion Model of Experimental Glaucoma in Brown-Norway Rats. [Thesis]. University of South Florida; 2018. Available from: https://scholarcommons.usf.edu/etd/7503

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Macquarie University

3. Chu, Edward Rickie Lim. Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions.

Degree: 2016, Macquarie University

Empirical thesis.

Bibliography: pages 66-80.

Chapter 1. Introduction  – Chapter 2. Materials and methods  – Chapter 3. Empirical insights into conventional outflow dynamics from an artificial hydraulic model  – Chapter 4. Understanding abnormal outflow resistance and episcleral venous pressure in an artificial hydraulic model of the conventional aqueous drainage  – Chapter 5. Limitations, conclusion and future directions.

Glaucoma is the leading cause of irreversible blindness in the world and remains a devastating ophthalmic condition. Current management seems limited and focuses mainly on reducing intraocular pressure. Glaucoma research models such as cell and organ based culture, computer simulation and animal models have played major roles in advancing the field, however, disease progression still occurs indicative that the pathophysiology of glaucoma has not been fully elucidated. In an attempt to shed some light into this issue, a novel artificial hydraulic model has been developed to empirically simulate fluid dynamics of the human conventional outflow pathway. Using non-biological materials, this model comprised of critical elements of the human aqueous outflow tract that include a microsyringe pump (simulating aqueous inflow/outflow), 35-gauge needle (stimulating trabecular meshwork), one way valve (simulating Schlemm’s canal inner wall endothelia) and a distal fluid column (simulating episcleral venous pressure) interconnected in between by pressure transducers and rigid tubings. The model was able to replicate various components of the conventional outflow pathway under physiological and pathological conditions. This system can potentially provide options to incorporate biological materials (i.e. cell cultures), include a parallel uveoscleral outflow system and/or simulate collector channel resistance to create a more comprehensive model to further our understanding in aqueous outflow dynamics.

1 online resource (80 pages) diagrams, graphs

Advisors/Committee Members: Macquarie University. Australian School of Advanced Medicine.

Subjects/Keywords: Glaucoma  – Treatment  – Research; Glaucoma  – Pathophysiology; artificiai simulation; model; aqueous humor dynamics; conventional outflow pathway; trabecular meshwork resistance; episcleral venous pressure; aqueous outflow pathology; glaucoma

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chu, E. R. L. (2016). Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions. (Masters Thesis). Macquarie University. Retrieved from http://hdl.handle.net/1959.14/1099821

Chicago Manual of Style (16th Edition):

Chu, Edward Rickie Lim. “Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions.” 2016. Masters Thesis, Macquarie University. Accessed November 21, 2019. http://hdl.handle.net/1959.14/1099821.

MLA Handbook (7th Edition):

Chu, Edward Rickie Lim. “Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions.” 2016. Web. 21 Nov 2019.

Vancouver:

Chu ERL. Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions. [Internet] [Masters thesis]. Macquarie University; 2016. [cited 2019 Nov 21]. Available from: http://hdl.handle.net/1959.14/1099821.

Council of Science Editors:

Chu ERL. Artificial simulation of th aqueous humor dynamics of the conventional outflow pathway under physiological and pathological conditions. [Masters Thesis]. Macquarie University; 2016. Available from: http://hdl.handle.net/1959.14/1099821

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