Targeting Transforming Growth Factor-ß Signaling in Primary Open-Angle Glaucoma.

Transforming growth factor-ß (TGF-ß) may play a role in the pathogenesis of primary open-angle glaucoma (POAG). Elevated levels of TGF-ß are found in the aqueous humor and in reactive optic nerve astrocytes in patients with glaucoma. In POAG, aqueous humor outflow resistance at the trabecular meshwork (TM) leads to increased intraocular pressure and retinal ganglion cell death. It is hypothesized that TGF-ß increases outflow resistance by altering extracellular matrix homeostasis and cell contractility in the TM through interactions with other proteins and signaling molecules. TGF-ß may also be involved in damage to the optic nerve head. Current available therapies for POAG focus exclusively on lowering intraocular pressure without addressing extracellular matrix homeostasis processes in the TM. The purpose of this review is to discuss possible therapeutic strategies targeting TGF-ß in the treatment of POAG. Herein, we describe the current understanding of the role of TGF-ß in POAG pathophysiology, and examine ways TGF-ß may be targeted at the levels of production, activation, downstream signaling, and homeostatic regulation.

The role of retrobulbar and retinal circulation on optic nerve head and retinal nerve fibre layer structure in patients with open-angle glaucoma over an 18-month period.

BACKGROUND/AIMS: Evidence suggests that vascular abnormalities play a role in the pathogenesis of open-angle glaucoma (OAG) in some patients. This study aims to assess changes in retrobulbar and retinal blood flow over time in patients with glaucoma and examine their relationship to glaucomatous progression, as determined by retinal and optic nerve structure. METHODS: In this observational study, 103 patients with OAG were examined at baseline and 18 months follow-up. Retrobulbar blood flow was measured by colour Doppler imaging in the ophthalmic, central retinal and temporal posterior ciliary artery (TPCA) and nasal short posterior ciliary artery. Retinal capillary blood flow was measured by confocal scanning laser Doppler. Peripapillary retinal nerve fibre layer thickness was assessed by optical coherence tomography. Non-parametric Wilcoxon signed ranks tests were used to assess for any statistically significant changes between the baseline and 18-month visits for the retrobulbar and retinal flow, as well as the structural parameters. RESULTS: In general, retinal and retrobulbar blood flow parameters decreased over 18 months. Thinning of the optic disc rim and increase in cup area were associated with a higher resistance index (p=0.0334) and lower peak systolic velocity of TPCA (p=0.0282), respectively. A higher amount of retinal zero pixel blood flow correlated with a greater increase in cup/disc ratio (p=0.0170). CONCLUSIONS: Reductions in retrobulbar and retinal blood flow over time were associated with structural glaucomatous progression, as indicated by retinal and optic nerve changes.

Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine.

The purpose of this review is to discuss the evolution of nanotechnology and its potential diagnostic and therapeutic applications in the field of ophthalmology, particularly as it pertains to glaucoma. We reviewed literature using MEDLINE and PubMed databases with the following search terms: glaucoma, nanotechnology, nanomedicine, nanoparticles, ophthalmology and liposomes. We also reviewed pertinent references from articles found in this search. A brief history of nanotechnology and nanomedicine will be covered, followed by a discussion of the advantages and concerns of using this technology in the field of glaucoma. We will look at various studies concerning the development of nanomedicine, its potential applications in ocular drug delivery, diagnostic and imaging modalities and, surgical techniques. In particular, the challenges of assuring safety and efficacy of nanomedicine will be examined. We conclude that nanotechnology offers a novel approach to expanding diagnostic, imaging and surgical modalities in glaucoma and may contribute to the knowledge of disease pathogenesis at a molecular level. However, more research is needed to better elucidate the mechanism of cellular entry, the potential for nanoparticle cytotoxicity and the assurance of clinical efficacy.

Novel therapies for open-angle glaucoma.

Open-angle glaucoma is a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells and their axons. It is an irreversible disease with no established cure. The only currently approved treatment is aimed at lowering intraocular pressure, the most significant risk factor known to date. However, it is now clear that there are other risk factors involved in glaucoma's pathophysiology. To achieve future improvements in glaucoma management, new approaches to therapies and novel targets must be developed. Such therapies may include new tissue targets for lowering intraocular pressure, molecules influencing ocular hemodynamics, and treatments providing neuroprotection of retinal ganglion cells. Furthermore, novel drug delivery systems are in development that may improve patient compliance, increase bioavailability, and decrease adverse side effects.

Retinal oxygen saturation and metabolism: how does it pertain to glaucoma? An update on the application of retinal oximetry in glaucoma.

PURPOSE: To discuss the techniques and mechanisms of retinal oximetry with a focus on utilization of retinal oximetry in the assessment of retinal oxygen saturation in glaucoma. METHODS: We reviewed recent literature found by searching combinations of the following search terms: glaucoma, retinal oximetry, ocular blood flow, retinal blood flow, oxygen saturation. We also reviewed pertinent references from articles found in this search. RESULTS: Retinal oximetry offers the potential for directly assessing oxygen saturation in retinal tissue. This capability can contribute to the knowledge of ocular blood flow and its role in the pathogenesis of glaucoma. CONCLUSIONS: Recent research has shown that retinal oximetry could become an important clinical tool in glaucoma. However, more research is needed to validate the reliability and reproducibility of retinal oximetry, and to fully deduce its clinical role in ocular diseases.

Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents.

Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.

Multiplexed nanoflares: mRNA detection in live cells.

We report the development of the multiplexed nanoflare, a nanoparticle agent that is capable of simultaneously detecting two distinct mRNA targets inside a living cell. These probes are spherical nucleic acid (SNA) gold nanoparticle (Au NP) conjugates consisting of densely packed and highly oriented oligonucleotide sequences, many of which are hybridized to a reporter with a distinct fluorophore label and each complementary to its corresponding mRNA target. When multiplexed nanoflares are exposed to their targets, they provide a sequence specific signal in both extra- and intracellular environments. Importantly, one of the targets can be used as an internal control, improving detection by accounting for cell-to-cell variations in nanoparticle uptake and background. Compared to single-component nanoflares, these structures allow one to determine more precisely relative mRNA levels in individual cells, improving cell sorting and quantification.