Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice.

Deficient Angiopoietin-Tie2 signaling is linked to ocular hypertension in glaucoma. Receptor Tie2/TEK expression and signaling at Schlemm's canal (SC) is indispensable for canal integrity and homeostatic regulation of aqueous humor outflow (AHO) and intraocular pressure (IOP), as validated by conditional deletion of Tie2, its ligands (Angpt1, Angpt2 and Angpt3/4) or regulators (Tie1 and PTPRB/VE-PTP). However, these Tie2/TEK knockouts and conditional knockouts are global or endothelial, preventing separation of systemic and ocular vascular defects that impact retinal or renal integrity.

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

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension.

Lentiviral vector-mediated expression of C3 transferase attenuates retinal ischemia and reperfusion injury in rats.

Aims: Our previous study showed that intravitreal delivery of self-complementary AAV2 (scAAV2)-mediated exoenzyme C3 transferase (C3) can attenuate retinal ischemia/reperfusion (I/R) injury. The current study investigated the neuroprotective effects of lentivirus (LV)-mediated C3 transgene expression on rat retinal I/R injury.

Main Methods: The LV encoding C3 and green fluorescent protein (GFP) together (LV-C3-GFP) or GFP only (LV-GFP) was intravitreally injected to SPRAGUE-DAWLEY rats.

Effects of Lentivirus-Mediated C3 Expression on Trabecular Meshwork Cells and Intraocular Pressure.

Purpose: We evaluated the effects of lentivirus-mediated exoenzyme C3 transferase (C3) expression on cultured primary human trabecular meshwork (HTM) cells in vitro, and on rat intraocular pressure (IOP).

Methods: HTM cells were cultured and treated with lentivirus vectors expressing either green fluorescent protein (GFP) only (LV-GFP) or GFP and C3 together (LV-C3-GFP). Changes in cell morphology and actin stress fibers were assessed.

AMBULATORY BLOOD PRESSURE PATTERNS IN PATIENTS WITH RETINAL VEIN OCCLUSION.

Purpose: Failure of blood pressure (BP) to dip during sleep (nondipper pattern) is associated with cardiovascular disease and stroke. The prevalence and degree of nondipping and masked hypertension in patients with retinal vein occlusion (RVO), which is associated with stroke, has not been previously examined.

Methods: We measured clinic and 24-hour ambulatory BPs in 22 patients with RVO and 20 control participants without known eye disease matched by age and sex.

A novel frameshift deletion in the COL1A1 gene identified in a Chinese family with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetically heterogeneous group of disorders, characterized by abnormal bone fragility, blue sclera, deafness, joint laxity, and soft-tissue dysplasia. The purpose of this study was to elucidate the genetic or molecular basis for OI type IA in a Chinese family. We evaluated the members of a family, in which six individuals are affected with increased bone fragility and blue sclera.

TGF-β2-mediated ocular hypertension is attenuated in SPARC-null mice.

Purpose: Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of primary open-angle glaucoma through extracellular matrix (ECM) alteration among various mechanisms. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates ECM within the trabecular meshwork (TM), and is highly upregulated by TGF-β2. We hypothesized that, in vivo, SPARC is a critical regulatory node in TGF-β2-mediated ocular hypertension.

Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.

Free-living amoebae of the Acanthamoeba species are the causative agent of Acanthamoeba keratitis (AK), a sight-threatening corneal infection that causes severe pain and a characteristic ring-shaped corneal infiltrate. Innate immune responses play an important role in resistance against AK. The aim of this study is to determine if Toll-like receptors (TLRs) on corneal epithelial cells are activated by Acanthamoeba, leading to initiation of inflammatory responses in the cornea.

Significance of arachidonic acid in ocular infections and inflammation.

Innate immune responses in the cornea mainly play an important role to mobilize multiple interrelated pathways of corneal lipid, which involve in inflammatory corneal diseases. Signaling lipid mediators derived from arachidonic acid (AA) control cell proliferation, apoptosis, metabolism, and migration, are known as eicosanoids, phosphoinositides, sphingolipids, and fatty acids. Emerging evidences have highlighted the implication of lipid mediators in both injury and repair mechanisms in the cornea.

Acute effects of calvarial damage on dural mast cells, pial vascular permeability, and cerebral cortical histamine levels in rats and mice.

Unlabelled: Neurological complications after mild head injury can include vasogenic edema and/or subsequent development of epilepsy, conditions associated with elevated histamine. In the present study we assessed the potential of mast cells located in the dura mater to contribute to elevated cortical histamine and breakdown of the blood-brain barrier after minor head injury, modeled by either a parietal craniectomy or producing a groove in (scoring) the parietal bone surface to model a grazing head injury. We measured the following effects at 5-20 min after a unilateral parietal craniectomy (rats) or unilateral scoring of the parietal bone (mice): (1) mast cell integrity in subjacent dura mater; (2) subjacent vs.

Activation of protein kinase C by tumor necrosis factor-alpha in human non-pigmented ciliary epithelium.

Previously, we have shown that tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, increases the synthesis and release of endothelin-1 (ET-1), a potent vasoactive peptide from human non-pigmented ciliary epithelial (HNPE) cells, in a protein kinase C (PKC)-dependent manner. Diacylglycerol (DAG) and intracellular calcium ([Ca2+]i) are well known activators of PKC. Some cytokines induce PKC activation by stimulating phospholipase C that hydrolyzes phosphatidylinositol bisphosphate (PIP2) into IP3 (intracellular calcium mobilizer) and DAG.

Immunolocalization of CD44 in the dystrophic rat retina.

The distribution of the cell surface adhesion/receptor molecule CD44 was studied in retinas of the Royal College of Surgeons (RCS) rat which exhibits an inherited retinal dystrophy. In this animal model, the retinal pigment epithelium fails to phagocytize shed photoreceptor outer segment material, a membranous debris layer accumulates in the subretinal space and the photoreceptor cells degenerate. Using immunoperoxidase and immunogold labeling, CD44 was localized to Müller cell apical microvilli in normal rat retinas, as noted in other species.

Possible involvement of Bcl-2 pathway in retinoid X receptor alpha-induced apoptosis of HL-60 cells.

Retinoids induce granulocytic differentiation and subsequent apoptosis in human myeloid (HL-60) leukemia cells. Differentiation is induced due to activation of retinoic acid receptors (RARs) whereas, activation of retinoid X receptors (RXRs) seems to be essential for driving these cells into apoptosis. In order to understand the mechanism of RXR induced apoptosis, we used a variant HL-60 cell line (HL-60R) with a transdominant negative mutation.