Oxygen and blood flow: players in the pathogenesis of glaucoma

The increase of IOP in POAG is due an increased resistance of aqueous outflow through the trabecular meshwork (TM). The exact mechanisms leading to the corresponding changes in the TM are not yet known. We know, however, that all risk factors for arteriosclerosis are also risk factors for an increase in IOP. RESULTS: The association between IOP increase and these factors is relatively weak but nevertheless significant. Similar to the pathogenesis of arteriosclerosis, oxidative stress plays a role in the development of TM damage. Even less is known about the pathogenesis of glaucomatous optic neuropathy (GON). Obviously the risk factors for arteriosclerosis play a role via increasing the IOP. When corrected for IOP, however, these factors only play a minor role. In contrast, factors associated with disturbed autoregulation, in particular a systemic primary vascular dysregulation (PVD), increase the risk for GON. This is best observed in normal tension glaucoma patients. An insufficient autoregulation increases the chance for an unstable ocular perfusion and thereby an unstable oxygen supply. This, in turn, leads to oxidative stress. The concentration of superoxide (O(2)(-)) within the axons of the optic nerve head increases. If neighboring astrocytes are activated, either by mechanical or by ischemic stress, in excess produced nitric oxide (NO) molecules diffuse also into the axons and fuse with oxygen. The resulting peroxynitrat (ONOO(-)) diffuses within the axons towards the retina and the lateral geniculate nucleus and induces apoptosis

The eye and the heart

The vasculature of the eye and the heart share several common characteristics. The easily accessible vessels of the eye are therefore—to some extent—a window to the heart. There is interplay between cardiovascular functions and risk factors and the occurrence and progression of many eye diseases. In particular, arteriovenous nipping, narrowing of retinal arteries, and the dilatation of retinal veins are important signs of increased cardiovascular risk. The pressure in the dilated veins is often markedly increased due to a dysregulation of venous outflow from the eye. Besides such morphological criteria, functional alterations might be even more relevant and may play an important role in future diagnostics. Via neurovascular coupling, flickering light dilates capillaries and small arterioles, thus inducing endothelium-dependent, flow-mediated dilation of larger retinal vessels. Risk factors for arteriosclerosis, such as dyslipidaemia, diabetes, or systemic hypertension, are also risk factors for eye diseases such as retinal arterial or retinal vein occlusions, cataracts, age-related macular degeneration, and increases in intraocular pressure (IOP). Functional alterations of blood flow are particularly relevant to the eye. The primary vascular dysregulation syndrome (PVD), which often includes systemic hypotension, is associated with disturbed autoregulation of ocular blood flow (OBF). Fluctuation of IOP on a high level or blood pressure on a low level leads to instable OBF and oxygen supply and therefore to oxidative stress, which is particularly involved in the pathogenesis of glaucomatous neuropathy. Vascular dysregulation also leads to a barrier dysfunction and thereby to small retinal haemorrhage

Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries

• Background: The present study was performed to investigate the influence of extracellular magnesium on changes in contractile tone induced by endothelin-1, and on relaxations to bradykinin in isolated porcine ciliary arteries. • Methods: Vessels were studied in a myograph system for measurement of isometric forces.Concentration-response curves (10−10-10−7 M) to endothelin-1 were constructed in the presence of different concentrations (0, 1.2, 2, 10 mM) of magnesium (MgSC4). Endothelin-1-precontracted vessels (∼10−8M) were exposed to magnesium (10−5-10−2 M) in the presence or absence of either the inhibitor of nitric oxide formation L-NAME (∼10−4 M), or different concentrations of calcium (2.5, 5, 10 mM). In endothelin-1-precontracted vessels (10−8 M), relaxations to bradykinin (10−10-10−6 M) were conducted in the presence of different concentrations of magnesium (0, 1.2, 10 mM). • Results: Contractions to endothelin-1 were reduced only in the presence of 10 mM magnesium. (1.2 mM vs 10 mM, P = 0.001). In endothelin-1 -precontracted vessels, magnesium evoked complete concentration-dependent relaxations (pD2 = 3.1 ± 0.1), which were shifted to the right by increasing extracellular concentrations of calcium (2.5 vs 5 mM, P<0.05). L-NAME had no influence on magnesium-induced relaxations. Relaxations to bradykinin remained unaffected by changes in extracellular magnesium concentrations. • Conclusions: In a mechanism which appears to be compatible with a calcium-antagonist effect, magnesium strongly modulates changes in contractile tone evoked by endothelin-1, but has no effect on bradykinin-induced relaxation

Short-term variability of systemic blood pressure and submacular choroidal blood flow in eyes of patients with primary open-angle glaucoma

Purpose: To analyse short-term variability of systemic blood pressure and choroidal blood flow in glaucoma patients, and compare them with ocular hypertensive patients and controls. Subjects and methods: Thirty untreated patients with primary open-angle glaucoma (POAG), 25untreated patients with ocular hypertension (OHT) and 50healthy controls without local therapy were included in the study. Continuous 5-minute measurements of arterial systemic blood pressure (SBP) by Finometer and choroidal blood flow (CBF) by laser Doppler flowmetry were obtained. Variability of SBP and CBF was analysed by means of coefficient of variation and analyzed in ANOVA model. Linear regression analysis was performed on parameters of morphological (nerve fiber layer thickness) and functional glaucomatous damage (visual field) on one side, and between SBP and CBF on the other side. Results: ANOVA model demonstrated significant differences in variability between the groups (p = 0.003); post-hoc analysis specified a significantly higher short-term variability of both the blood pressure and choroidal blood flow in POAG patients (coefficients of variation: 3.33% ± 1.05% and 3.90% ± 2.17% respectively) than in healthy controls (coefficient of variation: 2.57% ± 0.80% and 2.94% ± 1.52% respectively). No significant differences were found for OHT patients. Conclusions: POAG patients without local therapy demonstrate an increased short-term BP and CBF variabilit

Retinal vascular diameter in young subjects with a vasospastic propensity

Purpose: Retinal vascular diameters have recently been shown not to be related to an increased risk of open-angle glaucoma. Because vasospastic propensity has been suggested to represent a risk factor for various ocular diseases, especially glaucoma, the steady-state retinal vascular diameter in subjects with a propensity for systemic vascular dysregulation was compared with a group of age-matched gender-matched controls. Methods: Thirty healthy non-smoking individuals [female/male 26/4; mean±SD age 22.8±3.4 (range 18-31) years] were enrolled into the study. Subjects were classified as having vasospasm (15 subjects) if they related a clear history of frequently cold hands and as healthy subjects (15 subjects) if they denied such a history. Vasospastic propensity or the absence of it had to be confirmed by nail-fold capillaroscopy. Vascular diameter of retinal vessels was measured repeatedly on two days with the retinal vessel analyser and corrected for perfusion pressure, age, and refraction. Results: Neither retinal arteriole diameter (P=0.30) or retinal venule diameter (P=0.49), nor retinal arteriole-to-venule ratio (P=0.96), differed between the two experimental groups. Conclusions: Although vasospastic propensity has been suggested to represent a risk factor in various ocular diseases, the steady-state retinal vessel diameters are not altered in healthy vasospastic subjects. It is probable that the steady-state retinal vessel diameters are no adequate risk indicators for the haemodynamic risk in diseases such as glaucom

Smell perception in normal tension glaucoma patients

The aim of this study was to quantify the ability to identify odors in normal tension glaucoma (NTG) patients and healthy subjects with and without a primary vascular dysregulation (PVD)