Maneli Mozaffarieh

Autoregulation, a balancing act between supply and demand

Regulation of blood flow is necessary to adapt to different conditions. Regulation of ocular blood flow (OBF) compensates for varying perfusion pressures (autoregulation), adapts to the retinal activity (neurovascular coupling), and keeps the back of the eye at constant temperature (thermoregulation). While all vessels are under the control of the vascular endothelial cells, the retinal vessels are additionally under the control of the neural and glial cells, and the choroidal vessels are influenced by the autonomic nervous system. The optic nerve head is additionally controlled by circulating hormones. If the regulation does not occur according to the needs of the tissue, it is referred to as vascular dysregulation. Such a dysregulation can be secondary in nature, as, for example, in multiple sclerosis, in which the high level of endothelin reduces OBF. Dysregulation, however, can also occur without any underlying disease and is characterized by an inborn tendency to respond differently to various stimuli, such as cold temperatures or mechanical or emotional stress. The constellation of these features is known as primary vascular dysregulation (PVD). Subjects with PVD have disturbed autoregulation leading to an unstable OBF. This instability, in turn, induces a repeated mild reperfusion injury. The resulting oxidative stress contributes to the pathogenesis of glaucomatous optic neuropathy.

New insights in the pathogenesis and treatment of normal tension glaucoma

Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage and reducing IOP improves prognosis. Nevertheless, there is little doubt that other risk factors besides IOP such as unstable ocular perfusion are involved. Blood flow is unstable if either the IOP fluctuates at a high level (or blood pressure fluctuates at a low level) or if the autoregulation of blood flow disturbed. A common cause for a disturbed OBF autoregulation is a primary vascular dysregulation (PVD) frequently observed in normal tension glaucoma patients. An unstable blood flow leads to recurrent mild reperfusion injury (chronic oxidative stress) affecting particularly the mitochondria of the optic nerve head. OBF regulation can be improved by magnesium, calcium channel blockers as well as with carbonic anhydrase inhibitors.

The potential value of natural antioxidative treatment in glaucoma

Glaucomatous optic neuropathy implies loss of retinal ganglion cells, including their axons, and a major tissue remodeling, especially in the optic nerve head. Although increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, there is little doubt that other factors such as ocular blood flow play a role as well. Mechanisms leading to glaucomatous optic neuropathy are not yet clearly understood. There is, however, increasing evidence that both an activation of glial cells and an oxidative stress in the axons play an important role. Glial cells may be activated by mechanical stress via activation of the epidermal growth-factor-receptor, or by ischemic stress via an increase in endothelin. Several factors can systemically or locally increase oxidative stress. In glaucoma, an unstable ocular blood flow leading to repeated mild reperfusion seems to be most relevant in inducing oxidative stress. The simultaneous production of nitric oxide in the astrocytes and of superoxide in the mitochondria of the axons leads to the production of the damaging peroxynitrite. Therapeutically, we need to reduce intraocular pressure, stabilize ocular blood flow, and reduce oxidative stress. Various natural compounds possess potential antioxidative value. Reduction of oxidative stress at the level of mitochondria can be achieved by gingko biloba. Polyphenolic compounds, such as tea, red wine, dark chocolate, or coffee have antioxidative properties. Coffee contains 3-methyl-1,2-cyclopentanedione (MCP), capable of scavenging peroxynitirite. Red wine-polyphenols (e.g., resveratrol), exert vasoprotective effects by inhibiting the synthesis of endothelin-1. Dark chocolate decreases blood pressure and improves endothelium-dependant vasorelaxation. Anthocyanosides (bilberries) owe their antioxidant effects to their particular chemical structure. Other antioxidants include ubiquinone and melatonin.

Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population

BackgroundThe aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population.MethodsIn a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis.ResultsA total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs.ConclusionsThermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

Retinal vein occlusions: The potential impact of a dysregulation of the retinal veins.

A retinal vein occlusion (RVO) is a sight threatening disease. It can be divided into central vein occlusion and branch retinal vein occlusion. The pathogenesis of the condition remains to be solved. Mechanical compression of the vessel wall or thrombotic occlusion of the vessel lumen, sometimes combined with rheological disorders, are often assumed pathomechanisms. Accordingly, the therapy relies either on mechanical decompression, lyses of thrombi or improvement of rheology. A number of observations however, such as the relationship of RVO to atherosclerotic risk factors, spontaneous reversibility particularly in young patients, rest flow observed in angiography, occlusion despite anticoagulation or thrombocytopenia and finally the positive effect of anti-VEGF therapy are not explained by the present pathogenetic concept. As a new concept we propose a local venous constriction induced by vasoconstrictive molecules diffusing from neighbouring diseased arteries and/or from other neighbouring (hypoxic) tissues. Recognizing these postulated conditions might lead to an earlier identification of impending vein occlusions as well as to a treatment more tailored to the risk factor constellation of the particular patient.

A novel perspective on natural therapeutic approaches in glaucoma therapy

Glaucoma is becoming recognised as a condition for which not only elevated intraocular pressure (IOP), but also non-pressure-dependent risk factors, are responsible. Better knowledge of the pathogenesis has opened up new thera-peutic approaches that are often referred to as non-IOP-lowering treatment. These new avenues of treatment, some of which are still under investigation, include agents that can improve vascular regulation and blood flow to the eye and reduce oxidative stress. Vascular regulation can be improved systemically with magnesium. Dark chocolate and omega-3-fatty acids can also improve blood flow regulation. Oxidative stress at mitochondrial level can be reduced by gingko. Polyphenolic flavonoids (tea, coffee and red wine), anthocyanosides, ubiquinone and melatonin have antioxidant properties, and heat-shock proteins can be induced naturally by the use of sauna baths. Future intensive studies on the effect of these compounds may open up a new therapeutic era in glaucoma.

Half a pack of cigarettes a day more than doubles DNA breaks in circulating leukocytes

BackgroundThe mechanisms by which smoking induces damage is not known for all diseases. One mechanism believed to play a role is oxidative stress. Oxidative stress leads to cellular damage including DNA damage, particularly DNA breaks. We conducted this study to test the hypothesis that smokers have increased DNA breaks in their circulating leukocytes.MethodsA comparative quantification of single-stranded DNA breaks was performed by comet assay analysis in the circulating leukocytes of ten healthy smokers (average smoking rate: half a pack a day, range: 9-12 cigarettes a day) and ten age and sex matched healthy non-smokers. DNA breaks lead to smaller pieces of DNA, which migrate out of the nucleus forming a tail during gel-electrophoresis. Damage of an individual cell was quantified by the parameters tail moment and olive moment.ResultsSmoking had a clear effect on both study parameters (tail and olive moment). Smokers had more than double the amount of ss-DNA breaks in their circulating leukocytes than non-smokers [tail moment: 0·75 AU [smokers] compared to 0·2 AU [non-smokers]; olive moment: 0·85 AU [smokers] compared to 0·3 AU [non-smokers]; both p < 0·001].ConclusionSmoking half a pack a day interferes with DNA integrity. One potential explanation for the enhanced DNA breaks in smokers is oxidative stress.

The effect of flammer-syndrome on retinal venous pressure

BackgroundThe purpose of the study was to measure the retinal venous pressure (RVP) in the eyes of primary open-angle glaucoma (POAG) patients and healthy subjects with and without a Flammer-Syndrome (FS).MethodsRVP was measured in the following four groups of patients and age- and sex-matched healthy controls: (a) 15 patients with a POAG and a FS (POAG/FS+); (b) 15 patients with a POAG but without a FS (POAG/FS-); (c) 14 healthy subjects with a FS (healthy/FS+) and (d) 16 healthy subjects without a FS (healthy/FS-). RVP was measured in all participants bilaterally by means of contact lens ophthalmodynamometry. Ophthalmodynamometry is done by applying increasing pressure on the eye via a contact lens. The minimum force required to induce a venous pulsation is called ophthalmodynamometric force (ODF). The RVP is defined and calculated as the sum of ODF and intraocular pressure (IOP) [RVP = ODF + IOP].ResultsThe participants with a FS (whether patients with POAG or healthy subjects), had a significantly higher RVP compared to subjects without a FS (p = 0.0103). Patients with a POAG and FS (POAG/FS+) had a significantly higher RVP compared to patients without a FS (POAG/FS-) (p = 0.0301). There was a notable trend for a higher RVP in the healthy/FS + group compared to the healthy/FS - group, which did not reach statistical significance (p = 0.0898).ConclusionsRVP is higher in subjects with a FS, particularly in glaucoma patients. The causal relationship needs to be further evaluated.

Relationship between optic nerve head and finger blood flow.

Purpose To examine the relationship between optic nerve head (ONH) and finger blood flow in subjects with and without a primary vascular dysregulation (PVD). Methods ONH blood flow and finger blood flow was measured in 15 subjects with PVD and in 24 subjects without PVD. PVD was defined as being present if it was detected in patient history as well as by nailfold capillaromicroscopy PVD was defined as being absent if the patient history for PVD was negative and the results of nailfold capillaromicroscopy were negative. Scanning laser Doppler flowmetry (LDF) was used to measure ONH and finger blood flow. Finger temperature was measured in all subjects using a contact sensor. Results ONH blood flow is significantly related to finger blood flow in subjects with PVD (p<0.01), but not in subjects without a PVD. Subjects with PVD had a significantly lower finger skin temperature in comparison to those without PVD (p<0.01) Conclusions The present study indicates a relationship between ONH and finger blood flow in subjects with PVD. This might be an indirect sign of a disturbed autoregulation of ocular blood flow in PVD subjects.

Ocular blood flow and glaucomatous optic neuropathy

Ocular blood flow and glaucomatous optic neuropathy / , Ocular blood flow and glaucomatous optic neuropathy / , کتابخانه دیجیتال جندی شاپور اهواز