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Retinal blood flow autoregulation in response to an acute increase in blood pressure.

The response of the retinal circulation to an acute elevation in systemic blood pressure was studied in three healthy normotensive volunteers using the noninvasive laser Doppler velocimetry (LDV) technique combined with retinal vessel size measurements. Isometric exercise was employed to induce the acute rise in arterial pressure. There was no detectable change in retinal blood flow until the mean brachial artery blood pressure was elevated to an average of 115 mm Hg, which represented an average rise in mean blood pressure of 41% above baseline values. Above this value, blood flow increased along with further increments in blood pressure. The parallel rise between the ophthalmic artery pressure and the brachial artery pressure indicates that the regulation of retinal blood flow observed in the above mentioned pressure range is achieved through an increase in retinal vascular resistance rather than by a mechanism that would act to maintain a constant ocular perfusion pressure.

Adult↗

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

Adult↗

[The experimental study of octreotide suppressing retinal neovascularization].

OBJECTIVE: To study the effect and therapeutically role of octreotide on retinal neovascularization. METHOD: (1) Forty one-week-old mice were randomly divided into five groups, in which four groups were exposed to 75% oxygen to establish a model of retinal neovascularization, the other group were fed in the normal environment. Mice in control group did not receive any treatment. The two experimental groups were given acetate octreotide by subcutaneous injection at the dose of 20 microg.kg(-1) and 50 microg.kg(-1) respectively twice a day for five days while the control group was given sterile PBS subcutaneously. (2) The mice were sacrificed on 17-day, the eyes were enucleated for histological examination using light and electron microscopy. (3) The effect of acetate octreotide on retinal vessels formation was assessed by counting the number of endothelial cells of new vessels extending from retina to vitreous of 4 microm sagittal retinal cross sections under the light microscope. The expression of SSTR2 in the mice retina was determined by situ hybridization. The change of retinal ultrastructure was observed under the electron microscopy. RESULTS: (1) HE staining: The numbers of endothelial cells of new vessels extending form retina to vitreous in the experimental groups were much less than the control and hyperoxia group (P < 0.01). (2) Situ hybridization showed that SSTR2 expressed in the nurtroganglion layer, endothelial cells and inner nuclear layer in the normal, control and hyperoxia group while the octreotide treated retina showed only light positive staining of SSTR2 in the nurtroganglion layer. (3) Electron microscopy showed hypoxia caused the damage of photoreceptor cells but the damage abated considerably after the mice were treated by the octreotide. CONCLUSION: Subcutaneous injection of octreotide may suppress the retinal neovascularization in the mice oxygen model and provide some of protection from the damage of retinal ultrastructure.

Animals↗

Regional variation in capillary hemodynamics in the cat retina.

PURPOSE: The behavior of the retinal microcirculation and its role in the progression of ocular disease is of considerable interest, yet few details are known about the flow of blood through the capillary networks of the retina. Although retinal vessels may be viewed through the pupil using standard optics, the optical limitations of the cornea and lens prevent the resolution of retinal features smaller than approximately 10 microns in size. Because red blood cells are smaller than this, fluorescent techniques such as angiography, specific cell labeling, and fluorescein-encapsulated liposomes have typically been used to observe the retinal microcirculation in vivo. Here the authors report a study of in vivo retinal capillary hemodynamics using white light GRadient INdex of refraction (GRIN) lens endoscopy. METHODS: GRIN lens endoscopy and robotic manipulation were used to directly observe and record the motion of erythrocytes within retinal capillary networks. Video images from the endoscope were analyzed to determine the regional variation of erythrocyte velocity and normalized optical density (an index of relative capillary hematocrit) in the superficial retinal capillaries of the cat. RESULTS: A significant decrease in mean retinal capillary velocity coupled with a corresponding increase in red blood cell density was observed in peripheral regions of the retina when compared with regions of the retina near the optic disc. Stasis or intermittent flow was not observed in the unstained retina, nor were capillaries noted that contained only plasma. CONCLUSIONS: Quantification of the bloodflow in retinal microcirculation was possible using GRIN lens endoscopy and showed significant regional heterogeneity in the cat retina.

Animals↗

Experimental retinopathy by hyperbaric oxygenation.

Retinopathy of prematurity (ROP) usually occurs after a prolonged exposure to normobaric hyperoxia in newborn mammals and infants. We hypothesized that experimental ROP also could develop after acute exposures to hyperbaric oxygenation (HBO), providing that a severe and maintained retinal vasoconstriction occurred during HBO exposure. Five- to seven-day-old, Long Evans Sprague-Dawley rats were exposed for 5 h either to 5 atm abs oxygen or to 5 atm abs O2 with 190 mmHg inspired PCO2 (hypercapnia). Control rats breathed air at atmospheric pressure. Two months after exposures, rats were anesthetized, perfused intraventricularly with India ink, and retinal images were obtained. Retinal vascular density (RVD) in each image was calculated as the number of pixels in the retinal vessel area divided by the total number of pixels in the image (retinal tissue and vessels). The RVD was significantly increased from 0.0112 +/- 0.004 in the air-exposed controls to 0.0417 +/- 0.029 in the HBO-exposed rats (mean +/- SD; n = 4 in each group). HBO with hypercapnia produced a nonsignificant increase in RVD (0.0255 +/- 0.007; n = 4), reducing the HBO-induced increase in RVD by 39%. These results are consistent with the hypothesis that a sustained HBO-induced retinal vasoconstriction in newborn rats, followed by a hypoxic-ischemic injury, might result in vascular proliferation, thereby initiating ROP development on return to air. Hypercapnia does not completely prevent HBO-induced retinal vasoproliferation, probably because possible vasodilation, induced by hypercapnia, can greatly elevate retinal tissue PO2 and promote oxidative damage.

Animals↗

Inducible nitric oxide synthase subserves cholinergic vasodilation in retina.

In this paper, we investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of inducible (i) nitric oxide synthase (iNOS) expression and activity. The signaling pathway involved is also examined. These experiments also provide a link between mAChR activation and the nitric oxide (NO)-dependent regulation of retinal vascular diameter. The diameter of the retinal vessels at a distance of 1 disc diameter from the center of the optic disc was measured in rats using digital retinal photography, and both iNOS-mRNA gene expression and NOS were specifically measured using RT-PCR and [U-(14)C] citrulline assays, respectively. Stimulation of M(1) and M(3) mAChR with carbachol caused an increase in vessel diameter, in iNOS-mRNA levels and in NOS activity in the retina. Aminoguanidine, an inhibitor of iNOS, attenuated all these effects. Inhibitors of phospholipase C (PLC) and protein kinase C (PKC) but not calcium/calmodulin (CaM) prevented the muscarinic-dependent increase in iNOS-mRNA levels. The results obtained suggest that the activation of mAChR increases retinal vessel diameters by increasing the production of nitric oxide (NO) through iNOS activation and iNOS-mRNA gene expression. The mechanism appears to occur secondarily to stimulation of PLC and PKC enzymatic activity.

Animals↗

Retinal microvascular surgery: a feasibility study.

PURPOSE: To evaluate the feasibility of microvascular surgery at the level of the retinal vasculature. METHOD: Porcine eyes were used, and eyecups were prepared under an operating microscope. Several classic microvascular maneuvers were explored, such as vascular puncturing, catheterization, mobilization, intravascular injections, and various combinations of the same. Instruments used ranged from disposable 30-gauge needles to an Er:YAG laser. Commercially available 10-0 nylon sutures, fine polyimide tubes, and custom-made fine glass tubes were used for vascular catheterization. RESULTS: Puncturing, mobilization, catheterization, and intravascular injection of retinal arteries and veins were possible. The connection of two remote retinal vessels with a fine tube was also achieved with the combination of these maneuvers. CONCLUSIONS: The feasibility of performing several microvascular maneuvers on retinal arteries and veins was demonstrated in porcine eyes. Further experimentation and development of these findings in a living animal model could lead to the development of such microvascular maneuvers in humans.

Anastomosis, Surgical↗

A colobomatous optic disc anomaly and associated retinal detachement.

A case is presented of a two-year-old white female with an optic nerve anomaly and an associated retinal detachment. A unilateral colobomatous disc was noted to be surrounded by a chorioretinal pigmentary alteration in the form of an annulus. A clear zone with absence pigmentation ringed the more central gray-black area. The retinal vessels were noted to come directly out of the deeply colobomatous disc area and to run between the cystic convolutions of the adiacent retinal tissue. A surrounding area of retinal detachment extended for a distance of three disc diameters from the disc. This case is one of a few yet reported in the literature.

Child, Preschool↗

Unilateral retinitis pigmentosa with amblyopia in the fellow eye.

PURPOSE: The purpose was to report a case of unilateral retinitis pigmentosa with amblyopia in the other eye. METHODS: Eight years ago, a 36-year-old woman complained of peripheral visual field loss in her left eye when she covered her right eye. Complete ophthalmological examinations including fundus photography and fluorescein angiography, full-field electroretinography, dark adaptation, and microperimetry were performed. RESULTS: Best-corrected visual acuity of the patient was 0.2 with +2.5 diopters in her right eye and 0.3 with +1.5 diopters in her left eye. Fundus examination did not reveal any abnormalities in the right eye, but narrow retinal vessels, optic disc pallor, and peripheral retinal pigment clumping was found in the left eye. The full-field electroretinography was normal in the right eye, but rod response, cone response, and combined response were non-recordable, and 30-Hz response was very small in the left eye. Dark adaptation thresholds were normal in the right eye, but were dramatically elevated in the left eye. Microperimetry was normal in the right eye, but the visual field was reduced to a 2x5 degrees central field in the left eye. CONCLUSION: Unilateral retinitis pigmentosa with amblyopia in the other eye is a rare condition. The patient presented here had a case of unilateral retinitis pigmentosa with the other eye with ametropic amblyopia. It is necessary to perform functional and morphological ophthalmological examinations to confirm the diagnosis.

Adult↗

Proliferative sarcoid retinopathy.

Sarcoidosis is a well-established cause of ocular neovascularization. A review of the literature, however; shows that it has been implicated as the cause for retinal neovascularization in only a limited number of patients. In this article, the authors report the clinical features of proliferative sarcoid retinopathy in seven additional patients (11 eyes). All 11 eyes displayed retinal neovascularization. In addition, two of the eyes had optic disc neovascularization, whereas iris neovascularization developed in one. In all cases, the new retinal vessels were associated with concomitant peripheral retinal capillary nonperfusion. These findings support the theory that in sarcoidosis, capillary nonperfusion secondary to microvascular shutdown, rather than a direct effect of inflammation, is the stimulus for the formation of retinal neovascularization.

Adult↗

[Experimental fluorescence angiographic and microscopic investigations on laser treated animal eyes (author's transl)].

The effects of laser coagulation on rat fundi were studied angiographically and with the fluorescence microscope. The coagulations were performed using constantly 300 mW and 0.2 second exposure time and 50 microns spot diameter. We observed the animals for 3 months, after which we could still observe dye diffusion by fluorescence angiography. With the fluorescence microscope we could localize these diffusions as originating from neovascularisation starting from the choroid. These new vessels penetrated subsequently into the exterior retinal layers. At the beginning of our observation time, the retinal vessels showed some sinuosities, dilatations and solitary stenosis, but no disturbance of circulation was demonstrable.

Animals↗

Preserved vision despite distinct retinal edema in central retinal artery occlusion.

BACKGROUND: In subtotal central retinal artery occlusion (CRAO), distinct retinal edema with acute onset irreversible visual loss is common. - METHODS: Clinical observation, fluorescein angiogram. - PATIENT: A 69-year-old patient presented with acute visual loss of his right eye. Risk factors for CRAO were arterial hypertension and diabetes mellitus. A further factor was a 60% stenosis of the right and a 90% stenosis of the left internal carotid arteries. - RESULT: Visual acuity at initial examination was 20/32 despite pronounced central retinal edema with characteristic cherry red spot of the macula. Fluorescein angiography demonstrated early filling of retinal vessels, only perfusion of the inferior macular vessels was delayed. Two months later retinal edema resolved and central visual acuity was 20/25. - CONCLUSION: In this patient, retinal edema most likely resulted from a transient retinal ischemia. Spontaneous reperfusion occurred early enough to allow functional recovery in the ischemic retina.

Aged↗

Experimental ischemia induces cell mitosis in the adult rat retina.

Experimental occlusion of the central retinal vessels in albino rats followed by reperfusion for 2 or 4 days resulted in a highly active proliferative response. Mitotic figures were produced in retinal vascular cells, presumed Müller cells, retinal pigment epithelial cells, and possibly other cell populations in the retina. A large number of mitoses were observed in 60-100% of 50 experimental eyes with 2, 4 or 6 hr of experimental ischemia and 2 or 4 days of reperfusion and in none of the 37 control eyes. Autoradiography demonstrated 3H-thymidine uptake in the retina and in vascular cells on a trypsin digest preparation of the retina. Retinal ischemia followed by reperfusion leads to mitosis of retinal cells. This suggests a causal relationship in proliferative retinopathies where ischemia and cell proliferation coincide.

Animals↗

Retinal and central nervous system abnormalities: syndromes which resemble retrolental fibroplasia.

Recently, the mechanism of the development of severe retrolental fibroplasia has been shown to occur by gap junction formation between adjacent mesenchymal spindle cells in the nerve fiber layer. Multiple syndromes with oculo-cerebral malformations give rise to retinal dysplasia (disturbances of neuroectodermal migration and/or differentiation) or retinal vascular abnormalities (disturbances of mesenchymal differentiation) which resemble clinically retrolental fibroplasia. Case 1 is an example of retinal dysplasia (disturbed neuroectodermal migration and/or differentiation) with normal retinal vascularization simulating superficially an active peripheral retinal detachment of retrolental fibroplasia in the preterm infant. Case 2 is an example of normal retinal differentiation with abnormal retinal vascularization (disturbed mesenchymal differentiation) simulating identically cicatricial dragging of the retinal vessels temporally of retrolental fibroplasia in the preterm infant. Thus, cases of central nervous system malformation should prompt an early ophthalmologic examination to document retinal abnormalities in term infants which occur without the administration of oxygen congenitally, from true retrolental fibroplasia in preterm infants which occurs following changes in oxygen tension approximately 8 weeks postnatally.

Abnormalities, Multiple↗

Coats' disease and central nervous system venous malformation.

Primary retinal telangiectasis or Coats' disease is a non-hereditary retinal vascular abnormality consisting of incompetent telangiectatic and aneurysmal retinal vessels. It is characteristically found unilaterally in boys and occasionally may be associated with other systemic disorders. The authors report the first case of primary retinal telangiectasis with a concomitant diffuse central nervous system venous abnormality.

Aneurysm↗

Retinal hemodynamics after pars plana vitrectomy with silicone oil tamponade.

Pars plana vitrectomy with silicone-oil tamponade is frequently performed in cases of complicated retinal detachment. Because of the lower specific gravity and the lower surface tension of silicone oil in comparison with the aqueous phase of the vitreous, an influence on the blood flow in the retinal vessels would be expected. However, not only the silicone oil but also the operative trauma and a buckling procedure may have an influence on the retinal blood flow. To examine this question we measured the arteriovenous passage time in the silicone-oil-filled eye and in the contralateral eye in 14 cases using a laser scan ophthalmoscope at 3-5 days after surgery. The arteriovenous passage time is a parameter for the retinal microicirculation. In all cases we found a prolonged arteriovenous passage time in the silicone-oil-filled eye in comparison with the contralateral eye (mean value +/- SD, 2.5 +/- 0.8 vs 1.25 +/- 0.25 s; P < 0.01). The prolongation of arteriovenous passage times observed in silicone-oil-filled eyes indicates that the microcirculation is worsened at least during the early postoperative period.

Adult↗

Differential effect of Bordetella pertussis on experimental posterior uveitis in the black-hooded Lister rat.

The effect of an additional adjuvant, Bordetella pertussis, on the clinical and histopathologic features of experimental autoimmune uveitis in black-hooded Lister rats was investigated. Disease was induced by a single footpad injection of purified retinal S-antigen in Freund's complete adjuvant. In those animals that did not receive B Pertussis the clinical features were those of a retinal vasculitis with disc edema, periphlebitis, and deep retinal infiltrates. In contrast, animals that received B pertussis developed lesions in the pigment epithelium and choroid. Histopathologic studies disclosed focal photoreceptor necrosis associated with mononuclear cell infiltration in both groups of animals. However, in the group that did not receive B pertussis the disease was predominantly a retinitis associated with perivascular infiltration of retinal vessels, whereas in the group that did receive B pertussis the main feature was a focal choroiditis, with superficial retinal lesions being rarely observed. Retinal photoreceptors were the target tissue in both groups of rats, but the route by which they were damaged was altered from predominantly retinal to choroidal by the addition of Bordetella pertussis as an adjuvant. This change may be ascribed to the ability of B pertussis toxin to sensitize vascular endothelium to local mast cell products, these cells being plentiful around choroidal vessels but absent in the retinal circulation.

Adjuvants, Immunologic↗

Development of blood flow velocimeter for ocular vessels.

Clinical evidence suggests that blood flow in the retinal vessels varies in progressing diabetic retinopathy, coronary arteriole disease, hypertension and some other clinical situations. The changes of the flow in the blood vessels may serve as a monitor of the disease and as a follow up device for treatment success. Despite their importance direct blood flow velocity measurements are not easily obtainable. Recent advances in the development of a laser Doppler anemometry for the determination of in-vivo retinal blood velocity enables to obtain, with a noninvasive technique, information relevant to the flow of blood in the human retina. The described anemometry system is designed to be integrated, self-aligned and to operate with backscattered light. The influence of the important design parameters as well as focusing of the control volume on the retinal arteries is analyzed. Due to multiscattering of light from the blood cells present simultaneously in the control volume, the electronic signal obtained is very difficult to process and sophisticated signal processing routines are still being developed. At present measurements are used to obtain results with blood flowing in glass tubes of an inside diameter of 50 to 2000 microns. Preliminary experimental and theoretical simulations are currently being performed to validate the principle of the proposed data processing technique. Initial measurements have already produced relative high quality (and thus processable) signals, indicating good prospects for a practical ophthalmic system operation.

Blood Circulation↗