W. Daniel Stamer

Roles of exosomes in the normal and diseased eye.

Additionally, we discuss recent advances in the exosome field including use of exosomes as a therapeutic vehicle, exosomes as a source of biomarkers for disease, plus current standards for isolation and validation of exosome populations.

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.

President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology.

The vital role for nitric oxide in intraocular pressure homeostasis.

These IOP-dependent changes in the outflow pathway tissues reduce the resistance to aqueous humor drainage and lower IOP, which, in turn, diminishes the biomechanical signaling on SC.

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Chronic anti-VEGF injections significantly reduce outflow facility in patients with AMD.

A novel glaucoma approach: Stem cell regeneration of the trabecular meshwork.

Based on current knowledge of TM pathology in glaucoma and existing literature regarding stem cell regeneration of this tissue, we propose a human clinical study as the next step in understanding this potentially revolutionary treatment paradigm.

A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.

This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice.

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension.

Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.

In this article, we describe the current state of caveolin/caveolae research in the context of ocular function and pathophysiology. Finally, we discuss new evidence showing that retinal Cav1 exists and functions outside caveolae.

Expression of mRNAs, miRNAs, and lncRNAs in Human Trabecular Meshwork Cells Upon Mechanical Stretch.

To our knowledge, this is the first demonstration of the differential expression of coding and non-coding RNAs in a single set of cells subjected to cyclic mechanical stretch.

The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.

Breathing NO reduced IOP and increased outflow facility in a GC-dependent manner in mice. Exposure of ovine eyes to NO lowers IOP.

Reduced Oxidative Phosphorylation and Increased Glycolysis in Human Glaucoma Lamina Cribrosa Cells.

We demonstrate evidence of metabolic reprogramming (The Warburg effect) in glaucoma LC cells.

Greater Outflow Facility Increase After Targeted Trabecular Bypass in Angiographically Determined Low-low Regions.

Targeting surgery to low-flow areas of the trabecular meshwork yields higher overall facility increase and IOP reduction compared to surgery in high-flow areas.

Matrix Mechanotransduction via Yes-Associated Protein in Human Lamina Cribrosa Cells in Glaucoma.

These data demonstrate how YAP plays a pivotal role in LC cells adopting a profibrotic and proliferative phenotype in response to the stiffened LC present in aging and glaucoma.

Physiologic Consequences of Caveolin-1 Ablation in Conventional Outflow Endothelia.

Our results suggest that hyperactive eNOS signaling in the CO pathway of both Cav1ΔEC and global Cav1 knockout mice results in chronic dilation of distal CO vessels and protein nitration, but that Cav1 expression in…

lncRNAs, DNA Methylation, and the Pathobiology of Exfoliation Glaucoma.

This review briefly introduces the roles of long noncoding RNAs and DNA methylation in disease pathogenesis, and highlights some of the cutting edge work that has been carried out in PD and AD, along with the limited but important studies in XFG.

Optogenetic Modulation of Intraocular Pressure in a Glucocorticoid-Induced Ocular Hypertension Mouse Model.

Subcellular targeting of inositol phosphatases to remove PIP2 represents a promising strategy to reverse defective TM function in steroid-induced ocular hypertension.

Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.

Bimatoprost and BFA had differential effects on MMP/ECM gene expression.

ANGPTL7 and Its Role in IOP and Glaucoma.

Using multiple models, we have demonstrated that excess ANGPTL7 increases outflow resistance and IOP and that neutralizing ANGPTL7 has beneficial effects in both naïve and steroid-induced hypertensive eyes, thus motivating the development of ANGPTL7-targeting therapeutics…

The β4-Subunit of the Large-Conductance Potassium Ion Channel KCa1.1 Regulates Outflow Facility in Mice.

The β4-subunit regulates KCa1.1 activity in the conventional outflow pathway, significantly influencing outflow function. Targeting β4-containing KCa1.1 channels may be a promising approach to lower intraocular pressure to treat glaucoma.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

These include: (1) perfused whole globes, (2) stationary anterior segment organ culture, (3) perfused human anterior segment organ culture, (4) perfused animal anterior segment organ culture, (5) perfused human corneal rims, and (6) perfused human anterior segment wedges.

An In Vitro Bovine Cellular Model for Human Schlemm's Canal Endothelial Cells and Their Response to TGFβ Treatment.

Bovine AAP cells may serve as an alternative cellular model of human SC cells.

Scientific Concerns About Recent Fluid-Structure Interaction Models of the Aqueous Humor Outflow Pathway.

As a result, this body of work draws potentially misleading and erroneous conclusions about aqueous humor dynamics.

Anterior Segment Anatomy and Conventional Outflow Physiology of the Tree Shrew (Tupaia belangeri).

These studies lend support to the usefulness of the tree shrew as a novel animal model in anterior segment glaucoma and pharmacology research.

Pro-Homeostatic Effects of Estrogen on Intraocular Pressure and the Trabecular Meshwork.

These findings suggest that estrogen signaling promotes homeostatic TM regulation of IOP.

Left-Right Determination Factor 2 (LEFTY2) Is an Aqueous Humor Biomarker for Exfoliation Glaucoma.

LEFTY2 is a promising AH biomarker for XFG. Its clinical value may be limited by accessibility, OD/OS discordance, and interpatient variability. Its role in XFG pathogenesis requires further study.

Time-Dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal Cells.

This study identified candidate genes and pathways for glucocorticoid-induced ocular hypertension which can be further explored in human genetic analyses.

Intracameral Puncture Lowers Intraocular Pressure and Triggers an Immune Response in the Conventional Outflow Tract.

Coincident with significantly reduced IOP 1 day after ICP, there was an influx of macrophages into the distal portion of the conventional outflow tissues and a dilation of episcleral vessels, likely reducing distal outflow resistance.

Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.

Netarsudil acutely increased C by expansion of the JCT and dilating the ESVs, which led to redistribution of aqueous outflow through a larger area of the IW and ESVs.

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium.

Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes.

These data indicate that IWP-953, via modulation of the sGC-cGMP pathway, increases aqueous outflow facility in mouse eyes, suggesting therapeutic potential for sGC stimulators as novel ocular hypotensive drugs.

Expression Profiling of Human Schlemm's Canal Endothelial Cells From Eyes With and Without Glaucoma.

This study represents the first genome-wide expression study of human primary SC cells from glaucoma patients and provides a potential list of targets regulating SC cell stiffness and pore formation, eventually the outflow resistance in…

Implications of sustained elevation in extracellular ATP in retina following chronic ocular hypertension.

Aqueous humor outflow: dynamics and disease.

Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction.

Significantly, glaucomatous SC cells appear to be hyper-responsive to substrate stiffness. Thus, evidence suggests that targeting the material properties of SC cells will have therapeutic benefits for lowering intraocular pressure in glaucoma.