Acute hyperinsulinemia increases the contraction of retinal arterioles induced by elevated blood pressure.

Diabetic retinopathy is accompanied by disturbances in retinal blood flow, which is assumed to be related to the diabetic metabolic dysregulation. It has previously been shown that normoinsulinemic hyperglycemia has no effect on the diameter of retinal arterioles at rest and during an increase in the arterial blood pressure induced by isometric exercise. However, the influence of hyperinsulinemia on this response has not been studied in detail. In seven normal persons, the diameter response of retinal arterioles to an increased blood pressure induced by isometric exercise, to stimulation with flickering light, and to the combination of these stimuli was studied during euglycemic normoinsulinemia (protocol N) on one examination day, and euglycemic hyperinsulinemia (protocol H) on another examination day. Isometric exercise induced significant contraction of retinal arterioles at all examinations, but during a repeated examination the diameter response was significantly reduced in the test persons following the N protocol and increased in the persons following the H protocol. Flicker stimulation induced a significant dilatation of retinal arterioles at all examinations, and the response was significantly higher during a repeated examination, irrespective of the insulin level. Repeated exposure to isometric exercise reduces contraction, whereas repeated exposure to flickering light increases dilatation of retinal arterioles in vivo. Hyperinsulinemia increases contraction of retinal arterioles induced by isometric exercise.

[Complete ophthalmoplegia following outburst of herpes zoster]. / Komplet højresidig øjenmuskelparese efter herpes zoster-udbrud.

An 86-year-old female presented with eye pain, complete ophthalmoplegia, a visual acuity of 1/60, vitritis, ptosis, displacement of the eye, and a partially dilated pupil unresponsive to light. A computed tomography of the cerebrum was normal. Herpes zoster ophthalmicus was suspected and treatment with i.v. acyclovir and prednisolone was commenced, which led to a gradual improvement of the clinical condition. Complete ophthalmoplegia due to herpes zoster ophthalmicus is a very rare condition and no evidence-based treatment is available. The prognosis is very good with almost complete remission of the symptoms within 18 months.

The predictive value of subjective symptoms and clinical signs for the presence of treatment-requiring exudative age-related macular degeneration.

PURPOSE: The introduction of vascular endothelial growth factor inhibitors for the treatment of exudative age-related macular degeneration (AMD) has increased the referral rates of AMD patients with visual symptoms to treating centres considerably. However, a large proportion of the referred patients do not qualify for treatment implying that considerable resources could be saved if these patients could be identified on the basis of the clinical data available in the referring nonspecialized setting. METHODS: A prospective observational study of 1682 consecutive patients referred with suspicion of exudative AMD qualifying for intravitreal angiostatic treatment. On the basis of the structured interviewing about symptoms, ophthalmoscopy, optical coherence tomography scanning, and fluorescein angiography, the patients were divided into two groups: one qualifying for and another not qualifying for treatment. Multiple logistic regression was used to identify independent parameters predicting the need for treatment. RESULTS: The presence of metamorphopsia, dyschromatopsia, retinal haemorrhages and exudates, central retinal thickness, and the absence of micropsia were highly significant individual determinants of treatment-requiring AMD. Sudden onset and worsening of symptoms and the presence of a central dark spot covaried with the occurrence of retinal haemorrhages, whereas reduced visual acuity and blurred vision covaried with the presence of both haemorrhages and exudates. CONCLUSION: Patients with treatment-requiring AMD can be reliably identified by questioning about the presence of metamorphopsia and dyschromatopsia and the absence of micropsia, combined with ophthalmoscopical detection of retinal haemorrhages and exudates. This information may improve the triage of patients considered for referral.

The expression of STAT-1 and phosphorylated STAT-1 in conjunctival granulomas.

PURPOSE: Sarcoidosis is a granulomatous inflammatory disease whose cause is unknown. Based on gene expression profiles of peripheral blood and on immunostaining of lymph nodes from sarcoidosis patients, the authors recently implicated the transcription factor STAT-1 in the pathogenesis. They explored the potential contribution of STAT-1 in an ocular manifestation of this disease. METHODS: Conjunctival biopsies from 4 subjects with known sarcoidosis and from 8 subjects with conjunctival granulomas presumed from causes other than sarcoidosis were immunostained for STAT1. RESULTS: STAT-1 was readily detectable in all biopsies from patients with sarcoidosis and in 3 controls. The activated form of STAT-1, phosphorylated STAT-1, was also more frequently detected in tissue from subjects with sarcoidosis relative to controls. CONCLUSIONS: The activities of STAT-1 in regulating the inflammatory response suggest that it contributes to the conjunctival granulomas characteristic of sarcoidosis, but its expression is not specific for either sarcoidosis or all granulomatous conjunctival disease.

The vasodilating effect of acetazolamide and dorzolamide involves mechanisms other than carbonic anhydrase inhibition.

PURPOSE: Carbonic anhydrase inhibitors reduce intraocular pressure, which may protect the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to dilate the blood vessels in the retina and the optic nerve head. The purpose of the present study was to investigate whether CO(2), H(+), or factors other than carbonic anhydrase inhibition are involved in this vasodilating effect. METHODS: Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric force measurements. After precontraction with the prostaglandin analogue U46619, concentration-response experiments were performed with acetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were performed at normal pH and during acidosis, during normocapnia and hypercapnia, as well as in the nominal absence of CO(2) and HCO(3)(-). RESULTS: The maximum relaxation was significantly lower and the EC(50) significantly higher during normal pH compared with acidosis (P = 0.002 and P < 0.0001, respectively), but neither the maximum relaxation nor EC(50) was changed by hypercapnia (P = 0.054 and P = 0.57, respectively). The findings confirmed that carbonic anhydrase-induced vasodilation depends on the perivascular retinal tissue and that dorzolamide produces significantly more pronounced relaxation than does acetazolamide. EC(50) of carbonic anhydrase inhibitor-induced vasorelaxation and the maximum relaxation of dorzolamide were unchanged in the nominal absence of CO(2) and HCO(3)(-) (P = 0.65 and P < 0.0001, respectively). CONCLUSIONS: The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal arterioles depends on the perivascular retinal tissue and acidosis, but not on hypercapnia. The effect involves mechanisms other than carbonic anhydrase inhibition.

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N-methyl-D-aspartate and is blocked by prostaglandin synthesis inhibition.

PURPOSE: Retinal hyperperfusion resulting from disturbances in the regulation of arteriolar tone is involved in the pathophysiology of a variety of retinal diseases. The mechanisms underlying this regulation of tone involve cellular components in both the vascular wall and the perivascular tissue. However, previous in vitro studies of the influence of perivascular retinal tissue on retinal tone regulation have been hampered by the release of an endogenous relaxing factor that renders the arteriole insensitive to vasoconstrictors. The purpose of the present study was to test whether N-methyl-D-aspartate (NMDA) and gamma-amino butyric acid (GABA) receptors, and a cyclooxygenase (COX) product influence this effect of perivascular retinal tissue in vitro. METHODS: Porcine retinal arterioles were mounted in a wire myograph for isometric force measurements. The contractile effect of the prostaglandin analogue U46619 was studied on vessels with preserved perivascular retinal tissue and after this tissue had been removed. The influence of the perivascular tissue was studied after addition of NMDA (a specific agonist for a subtype of the glutamate receptor), DL-amino-5-phosphonovaleric acid (DL-APV, an antagonist at the same receptor), the natural inhibitory transmitter GABA, and picrotoxin (an antagonist at ionotropic GABA receptors). These experiments were made in the absence and presence of the COX inhibitor, ibuprofen. RESULTS: U46619 caused a concentration-dependent contraction of isolated retinal arterioles. This vasoconstriction was significantly smaller in the presence of perivascular tissue. The NMDA-receptor antagonist, DL-APV, reduced this attenuating influence of the perivascular tissue on the response to U46619, and the response could be modified by NMDA and GABA, but not by picrotoxin. However, ibuprofen totally blocked the attenuating influence of the perivascular tissue on the response to U46619. CONCLUSIONS: The inhibition of vascular contractility induced by perivascular retinal tissue in vitro involves NMDA-receptors and an effect of GABA-mimetic substance on retinal tissue. The generation of these effects involves a COX product.

Variable involvement of the perivascular retinal tissue in carbonic anhydrase inhibitor induced relaxation of porcine retinal arterioles in vitro.

PURPOSE: Inhibition of carbonic anhydrase in the eye is an important treatment modality for reducing the intraocular pressure in glaucoma. However, evidence suggests that carbonic anhydrase inhibition also exerts a relaxing effect on the vessels in the optic nerve, and it has been suggested that this vasorelaxing effect is a result of an interplay between the perivascular tissue and constituents in the retinal vascular wall. However, the exact nature of this interplay is unknown. METHODS: Isolated porcine retinal arterioles and arterioles with preserved perivascular retinal tissue were mounted in a myograph. After precontraction with the prostaglandin analogue U46619, the vasorelaxing effect of the carbonic anhydrase inhibitors methyl bromopyruvate, ethyl bromopyruvate, acetazolamide, and dorzolamide were studied. RESULTS: All the examined carbonic anhydrase inhibitors induced a significant relaxation of retinal arterioles. There was no significant difference between the effect of the different carbonic anhydrase inhibitors in the presence of perivascular retinal tissue. However, in the isolated retinal arterioles the vasodilating effect of dorzolamide was significantly lower, and the vasodilating effect of acetazolamide almost disappeared. CONCLUSIONS: A further elucidation of the mechanisms of action of carbonic anhydrase-induced dilation of retinal arterioles may contribute to a better understanding of the regulation of retinal blood flow. The perivascular retinal tissue may play a significant role in diameter control of retinal arterioles.

Effect of acidosis on isolated porcine retinal vessels.

PURPOSE: To study the effect of normocapnic (NA) and hypercapnic acidosis (HA) on the tone, the intracellular calcium level ([Ca(2 +)](i)), and the membrane potential of smooth muscle cells in porcine retinal arterioles. METHODS: Twenty-four porcine retinal arterioles were mounted in a wire myograph for isometric recording of the wall tension. The vessels were precontracted with 0.3 microM U46619 and were exposed to NA (pH = 7.0) and HA (pH = 7.0). Intracellular calcium was measured using the fluorophore Fura-2AM (n = 12). In six vessels, 0.1 mM NG-nitroarginine methyl ester (L-NAME) was added to block NO synthesis. The membrane potential of smooth muscles cells was measured in situ with sharp glass electrodes (n = 12). RESULTS: NA and HA induced both a decrease in wall tension from 1.04 +/- 0.06 N/m to 0.65 +/- 0.1 N/m (p < 0.01) (NA) and 0.56 +/- 0.1 N/m (p < 0.01) (HA) and a decrease in [Ca(2 +)](i) as evidenced from the change in the Fura-2 fluorescence emission ratio from 0.66 +/- 0.03 to 0.57 +/- 0.05 (p = 0.005) (NA) and 0.56 +/- 0.05 (p = 0.002) (HA). These results were unaffected by inhibition of NO-synthesis. NA and HA also both induced hyperpolarization of the smooth muscle membrane from -18 +/- 0.7 mV during precontraction to -26 +/- 1.9 mV (p = 0.002) (NA) and -24 +/- 2.6 mV (p = 0.02) (HA). CONCLUSIONS: Acidosis-induced relaxation of the tone in preconstricted isolated porcine retinal arterioles is associated with a decrease in intracellular calcium and a hyperpolarization of the smooth muscle cells. The acidosis-induced relaxation is independent of CO(2) and is not mediated through NO.

Effect of cyclic guanosine-monophosphate on porcine retinal vasomotion.

PURPOSE: Vasomotion refers to periodic oscillations in vascular tone that ensure the intermittent supply of blood to adjacent microvascular units. Previous evidence from vessels outside the eye suggests that cyclic guanosine-monophosphate (cGMP) is involved in the regulation of vasomotion, but it is unknown whether this compound has an effect on vasomotion in retinal vessels. METHODS: Retinal arterioles from porcine eyes were studied in a wire myograph. After initiation of vasomotion, the vessels were stimulated with increasing concentrations of the cGMP agonist 8-Br-cGMP (n = 6), the phosphodiesterase inhibitor zaprinast (n = 6) and the cGMP synthesis inhibitor L-NAME (n = 6). High concentrations of L-NAME blocked vasomotion, and control experiments (n = 20) using 8-Br-cGMP, S-nitroso-N-acetylpenicillamine (SNAP), adenosine and pinacidil were carried out to elucidate whether this effect was related to changes in the general tone of the vessel. Additionally, the relationship between oscillations in vascular tone and intracellular calcium concentration was studied. RESULTS: Induction of cGMP agonistic activity with either 8-Br-cGMP or zaprinast lowered the vasomotion frequency significantly, whereas L-NAME-induced inhibition of cGMP increased this frequency. Neither of the agents affected the amplitude of the oscillations. The control experiments indicated that the effect of cGMP on vasomotion frequency was independent of the accompanying increase in tone. The oscillations in tone during vasomotion were accompanied by similar oscillations in intracellular calcium concentration. CONCLUSION: Cyclic GMP lowers the frequency without affecting the amplitude of vasomotion in isolated porcine retinal arterioles.

Characterization of vasomotion in porcine retinal arterioles.

PURPOSE: To characterize vasomotion in porcine retinal arterioles in vitro using isobaric (pressure myograph) and isometric (wire myograph) methods. METHODS: Pressure myograph: 208 small porcine retinal arterioles (outer diameter 68 +/- 4 microm) were studied under isobaric conditions in a double-barrelled pipette system. Diameter changes of the arterioles were registered by video recordings. Wire myograph: 60 large porcine retinal arterioles (inner diameter 147 +/- 1.6 microm) were studied under isometric conditions in a small vessel myograph for force measurements. RESULTS: The rates of success in initiating vasomotion were 7.2% using the pressure myograph and 43% using the wire myograph (p < 0.001). The small vessels studied under isobaric conditions oscillated with a frequency of 0.014 Hz and the episodes lasted 6.0 +/- 1.0 min, whereas the large vessels under isometric conditions oscillated with a significantly faster frequency of 0.043 Hz and lasted 32.1 +/- 4.9 min (p = 0.026). CONCLUSION: Retinal vasomotion can be studied in vitro using both pressure myograph and wire myograph techniques. The wire myograph is superior to the pressure myograph in initiating and maintaining vasomotion in vitro.