Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.

Retinal neurodegenerative diseases, including hypertensive retinopathy, involve progressive damage to retinal neurons, leading to visual impairment. In this study, we investigated the pathological mechanisms underlying retinal neurodegeneration in spontaneously hypertensive rats (SHR), using Wistar Kyoto (WKY) rats as normotensive controls. We observed that SHR exhibited significantly higher blood pressure and decreased retinal thickness, indicating retinal neurodegeneration.

High Glucose Induces Oxidative Stress That Alters Glycocalyx Proteoglycan Levels in Primary Rat Retinal Microvascular Endothelial Cells and in Isolated Ophthalmic Arteries.

Our purpose in this study was to identify the role played by oxidative stress in the changes to proteoglycans that occur under hyperglycemic conditions, using primary rat retinal microvascular endothelial cells (RRMEC) and cultured ophthalmic arteries. The cells and blood vessels obtained from rats were cultured in normal glucose (5.6 mM) and high glucose (25 mM) with or without N-acetylcysteine (NAC), an antioxidant.

Decreased retinal and choroidal endothelial surface molecules in spontaneously hypertensive rats.

Hypertension is associated with changes in the retina and choroid, with resulting consequences of increased vascular permeability and microhemorrhages. To date, very little information is available regarding the changes in the retinal and choroidal endothelial surface layer. In this study, we have examined changes in protein expression of several molecules including platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial cadherin (VE-cadherin), glypican-1, and syndecan-1, in spontaneously hypertensive rats (SHR) compared to control normotensive Wistar Kyoto (WKY) rats.

Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.

The endothelial glycocalyx (EG) is a meshlike network present on the apical surface of the endothelium. Membrane-bound proteoglycans, the major backbone molecules of the EG, consist of glycosaminoglycans attached to core proteins. In addition to maintaining the integrity of the endothelial barrier, the EG regulates inflammation and perfusion and acts as a mechanosensor.

The Endothelial Glycocalyx and Retinal Hemodynamics.

Purpose: Previous studies suggest that the endothelial glycocalyx adds to vascular resistance, inhibits thrombosis, and is critical for regulating homogeneous blood flow and ensuring uniform red blood cell (RBC) distribution. However, these functions and consequences of the glycocalyx have not been examined in the retina. We hypothesize that the endothelial glycocalyx is a critical regulator of retinal hemodynamics and perfusion and decreases the propensity for retinal thrombus formation.

Effect of high glucose on glycosaminoglycans in cultured retinal endothelial cells and rat retina.

Introduction: The endothelial glycocalyx regulates vascular permeability, inflammation, and coagulation, and acts as a mechanosensor. The loss of glycocalyx can cause endothelial injury and contribute to several microvascular complications and, therefore, may promote diabetic retinopathy. Studies have shown a partial loss of retinal glycocalyx in diabetes, but with few molecular details of the changes in glycosaminoglycan (GAG) composition.

Candesartan Normalizes Changes in Retinal Blood Flow and p22phox in the Diabetic Rat Retina.

Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ).

Hyperglycemia-induced effects on glycocalyx components in the retina.

Purpose: Diabetic retinopathy is a vision-threatening complication of diabetes characterized by endothelial injury and vascular dysfunction. The loss of the endothelial glycocalyx, a dynamic layer lining all endothelial cells, contributes to several microvascular pathologies, including an increase in vascular permeability, leukocyte plugging, and capillary occlusion, and may drive the progression of retinopathy. Previously, a significant decrease in glycocalyx thickness has been observed in diabetic retinas.

The role of tumor necrosis factor-α and interferon-γ in the hyperglycemia-induced ubiquitination and loss of platelet endothelial cell adhesion molecule-1 in rat retinal endothelial cells.

Objective: This study aimed to investigate the role of the hyperglycemia-induced increase in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the ubiquitination and degradation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in the diabetic retina.

Methods: Type I diabetes was induced in rats by the injection of streptozotocin, with age-matched non-diabetic rats as controls. Primary rat retinal microvascular endothelial cells were grown in normal or high glucose media for 6 days or in normal glucose media for 24 h with addition of TNF-α and/or IFN-γ.

Retinal hypoxia and angiogenesis with methamphetamine.

Central retinal artery occlusion, retinopathy, and retinal neovascularization have been reported in methamphetamine (METH) abusers. In the current study, we investigated whether METH induces retinal neovascularization in a mouse model, and if so, whether the neovascularization is associated with increased hypoxia, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF). Mice were administrated METH by intraperitoneal injection over a 26-day period, or injected with saline as a vehicle control.

Retinal Physiology and Circulation: Effect of Diabetes.

In this article, we present a discussion of diabetes and its complications, including the macrovascular and microvascular effects, with the latter of consequence to the retina. We will discuss the anatomy and physiology of the retina, including aspects of metabolism and mechanisms of oxygenation, with the latter accomplished via a combination of the retinal and choroidal blood circulations. Both of these vasculatures are altered in diabetes, with the retinal circulation intimately involved in the pathology of diabetic retinopathy.

Altered Retinal Hemodynamics and Mean Circulation Time in Spontaneously Hypertensive Rats.

Purpose: Although it is known that the retinal arteriolar vasculature is constricted in hypertension, the details of retinal hemodynamics and perfusion of the retinal circulation have yet to be adequately characterized.

Methods: Male and female spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls were anesthetized before measurements of mean arterial blood pressure and preparation for intravital microscopy of the retinal microcirculation. Retinal vascular velocities were measured with the use of fluorescent microspheres, and diameters and mean circulation times were measured after the infusion of fluorescent dextran.

Acute changes in the retina and central retinal artery with methamphetamine.

Methamphetamine (METH), an addictive stimulant of neurotransmitters, is associated with cardiovascular and neurological diseases. METH-induced ophthalmic complications are also present but have been insufficiently investigated. The purpose of this study is to investigate the retinal effects of METH.

Hyperglycemia-induced ubiquitination and degradation of β-catenin with the loss of platelet endothelial cell adhesion molecule-1 in retinal endothelial cells.

Objective: Increased retinal vascular permeability is one of the earliest manifestations of diabetic retinopathy. The aim of this study was to investigate the role of hyperglycemia-induced platelet endothelial cell adhesion molecule-1 loss on retinal vascular permeability via the β-catenin pathway.

Methods: Type I diabetes was induced in male Wistar rats using streptozotocin injections, with age-matched non-diabetic rats as controls.

Blood flow distribution and the endothelial surface layer in the diabetic retina.

Diabetic retinopathy is known as a microvascular complication of hyperglycemia, with a breakdown of the blood-retinal barrier, loss of pericytes, formation of microhemorrhages, early decreases in perfusion and areas of ischemia, with the latter speculated to induce the eventual proliferative, angiogenic phase of the disease. Our animal models of diabetic retinopathy demonstrate similar decreases in retinal blood flow as seen in the early stages of diabetes in humans. Our studies also show an alteration in the retinal distribution of red blood cells, with the deep capillary layer receiving a reduced fraction, and with flow being diverted more towards the superficial vascular layer.

Loss of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) in the Diabetic Retina: Role of Matrix Metalloproteinases.

Purpose: To test the hypothesis that high glucose and matrix metalloproteinases (MMPs) contribute to the diabetes-induced loss of platelet endothelial cell adhesion molecule-1 (PECAM-1) in the retinal microvasculature.

Methods: PECAM-1 and MMP protein, activity, and interactions with PECAM-1 were assessed using western blotting, zymography, immunofluorescence, or coimmunoprecipitation assays. These assays were conducted using primary rat retinal microvascular endothelial cells (RRMECs) grown either in normal glucose (5 mM) or high glucose (25 mM) conditions and using retinas collected from streptozotocin-induced diabetic or control rats.

Diabetic retinopathy: Breaking the barrier.

Diabetic retinopathy (DR) remains a major complication of diabetes and a leading cause of blindness among adults worldwide. DR is a progressive disease affecting both type I and type II diabetic patients at any stage of the disease, and targets the retinal microvasculature. DR results from multiple biochemical, molecular and pathophysiological changes to the retinal vasculature, which affect both microcirculatory functions and ultimately photoreceptor function.

The Assembly and Application of 'Shear Rings': A Novel Endothelial Model for Orbital, Unidirectional and Periodic Fluid Flow and Shear Stress.

Deviations from normal levels and patterns of vascular fluid shear play important roles in vascular physiology and pathophysiology by inducing adaptive as well as pathological changes in endothelial phenotype and gene expression. In particular, maladaptive effects of periodic, unidirectional flow induced shear stress can trigger a variety of effects on several vascular cell types, particularly endothelial cells. While by now endothelial cells from diverse anatomic origins have been cultured, in-depth analyses of their responses to fluid shear have been hampered by the relative complexity of shear models (e.

Anemia and retinal function in a mouse model of acute colitis.

Individuals with inflammatory bowel diseases (IBD) have an elevated risk of ocular inflammation. Both the anterior and posterior eye can be affected by IBD, although posterior eye dysfunction is more likely to go undetected. Little investigative attention has been directed toward the mechanisms of ocular dysfunction with IBD; however, given the prevalence of anemia in IBD and the effects of anemia on the retina, we examined the association between retinal function (electroretinography, ERG) and the anemia induced by experimental IBD, and we tested for a potential retinal benefit of acutely attenuating anemia (via red blood cell (RBC) infusion).

Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy.

Retinal tissue receives its supply of oxygen from two sources - the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death.

Intravital video microscopy measurements of retinal blood flow in mice.

Alterations in retinal blood flow can contribute to, or be a consequence of, ocular disease and visual dysfunction. Therefore, quantitation of altered perfusion can aid research into the mechanisms of retinal pathologies. Intravital video microscopy of fluorescent tracers can be used to measure vascular diameters and bloodstream velocities of the retinal vasculature, specifically the arterioles branching from the central retinal artery and of the venules leading into the central retinal vein.

Ocular dysfunction in a mouse model of chronic gut inflammation.

Background: Ocular disease is known widely to occur in a subset of patients experiencing inflammatory bowel diseases. Although this extraintestinal manifestation has been recognized for a number of years, the pathogenetic mechanisms responsible for this distant organ inflammatory response are unknown.

Methods: In the current study, we used a T-cell transfer model of chronic colitis in mice in which we quantified colonic inflammation, ocular function (electroretinography), ocular blood flow (intravital microscopy of the retina), intraocular pressure, and retinal hypoxia.

Decreased retinal blood flow in experimental colitis; improvement by eye drop administration of losartan.

Patients with inflammatory bowel disease suffer not only from gut inflammation, but also from extraintestinal manifestations of the disease, including ocular pathology. The mechanisms causing ocular inflammation in these patients are unknown. The purpose of the current study was to investigate the possible vascular changes occurring in the retina using a mouse model of acute colitis, that is, ingestion of dextran sodium sulfate (DSS).

Measurement of retinal blood flow rate in diabetic rats: disparity between techniques due to redistribution of flow.

Purpose: Reports of altered retinal blood flow in experimental models of type I diabetes have provided contrasting results, which leads to some confusion as to whether flow is increased or decreased. The purpose of our study was to evaluate early diabetes-induced changes in retinal blood flow in diabetic rats, using two distinctly different methods.

Methods: Diabetes was induced by injection of streptozotocin (STZ), and retinal blood flow rate was measured under anesthesia by a microsphere infusion technique, or by an index of flow based on the mean circulation time between arterioles and venules.