[Histochemical studies of retinal blood vessels].
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OBJECTIVE: It is unclear if estrogen replacement therapy (ERT) has an effect on the retinal circulation. In the current study, we examine the association of ERT, female reproductive factors, and retinal vascular caliber. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Women participants aged 43 to 84 years living in Beaver Dam, Wisconsin. METHODS: Retinal photographs of participants taken at the baseline examination were digitized, and the diameters of arterioles and venules were measured using a well-established technique. Estrogen replacement therapy and female reproductive factors were ascertained by interview. MAIN OUTCOME MEASURES: Retinal arteriolar and venular diameters. RESULTS: Of the 2469 women participants with data for analysis, 10.5% were current users of ERT and 7.4% were past users. After adjusting for age, blood pressure (BP), body mass index, smoking, and other factors, women who were current users of ERT had narrower retinal arteriolar and venular diameters than those who were past users or never used, with mean arteriolar diameters of 167.6 microm for current users, 170.8 microm for past users, and 170.9 microm for those who never used (P = 0.009) and mean venular diameters of 239.9 microm for current users, 244.0 microm for past users, and 243.9 microm for those who never used (P = 0.02). There was a significant trend of increasing narrowing for both arterioles (P trend, 0.01) and venules (P trend, 0.007) with increasing duration of ERT. Associations were somewhat stronger in younger women and women without a history of hypertension and cigarette smoking. Female reproductive factors (e.g., age of menarche and pregnancy) were not associated with retinal vessel diameters. CONCLUSIONS: Estrogen replacement therapy is associated with narrower retinal vessel diameters, independent of BP and other vascular factors.
It has been proposed that oxidative tissue damage is involved in the development of diabetic angiopathies. To evaluate this hypothesis, experiments were conducted to identify the retinal vessel changes induced by the oxidative stress related to alpha-tocopherol deficiency and examine possible similarities with the lesions characteristic of diabetic retinopathy. Twenty-one-day-old male Fisher 344 albino rats were divided randomly to receive a basal, chemically defined diet either with (adequate group) or without (deficient group) alpha-tocopherol. After 6 and 8 months, some rats (n = 3 per group) were killed and the eyes removed. In order to evaluate cell integrity and localization of lipofuscin-specific autofluorescence by light and fluorescence microscopy, some of the retinas were prepared for cryostat-sections while others were digested by elastase to isolate intact retinal vasculatures. After 8 and 14 months, the central retina of one eye per rat (n = 6 to 8 per group) was examined by electron microscopy for retinal capillary basement membrane (RCBM) thickening and other ultrastructural changes. At 6 and 8 months, the deficient rats exhibited extensive shortening and disarray of rod outer segments (ROS), marked loss of photoreceptor cells, and pronounced increases in the numbers of granules with lipofuscin-specific autofluorescence in the retinal pigment epithelium (RPE) and retinal vessels. At 14 months, the ultrastructure revealed that the damage to ROS involved disruption of membranes and that the capillary lipofuscin was contained mainly within the endothelial cells. Membrane remnants were found in the lipofuscin granules of both the RPE and retinal vessels. In addition, there was an increase in RCBM thickness (98.7 +/- 2.6 nm vs. 86.9 +/- 2.9 nm). RCBM thickening was the only finding common with diabetic retinopathy, and the thickening was 13.6%, significantly less than that reported in diabetic rat models with 8 and 14 months durations (34% and 53.1%, respectively). Capillary lipofuscin accumulation, which was prominent in the deficient rats, is not notable in diabetes. Both the moderate RCBM thickening and marked lipofuscin accumulations seen in alpha-tocopherol-deficient rats were similar to changes occurring in the aging process, though more pronounced. The spectrum of microangiopathies characteristic of diabetic retinopathy did not develop in alpha-tocopherol-deficient rats. These findings suggest that oxidative damage, though probably involved, is unlikely to play a predominant role in the development of diabetic retinal microangiopathies.
The largest arteries in the rat retina are the arterioles in the nerve fiber layer adjacent to the optic papilla. They are 50 to 100 micrometer in diameter, have an incomplete internal elastic lamina and usually a single layer of smooth muscle. Smaller arterioles of 10 to 50 micrometer have no internal elastic lamina and the media is formed by one or two layers of slender smooth muscle cells. In these vessels, myoendothelial junctions and close contact areas between smooth muscle cells are numerous. Capillaries are present in all layers of the rat retina and from plexuses in the nerve fiber, outer plexiform and exterior part of the inner plexiform layers. In nearly all capillaries, pericytes and their processes from a single layer external to the endothelium with numerous contact points or zones between endothelium and pericytes without any intervening basal laminar material. Areas of close contact between adjacent pericyte processes are frequent. The possible functions of myoendothelial junctions and pericyte-endothelial contacts in relation to vessel tone, mechanical stabilization and metabolic exchange are discussed.
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In Royal College of Surgeons (RCS) rats, the defective retinal pigment epithelium (RPE) fails to phagocytose the shed outer segment membranes, and the photoreceptors degenerate. Following degeneration of the photoreceptors, neovascularization and vitreo-retinal membranes (VRMs) develop. Blood-retinal barrier abnormalities at the level of the RPE suggested that Bruch's membrane extracellular matrix filtration barriers might also be abnormal. To study the progression of RPE cell, extracellular matrix and vascular alterations in the dystrophic retina, we used the cationic tracer polyethyleneimine and electron microscope morphometric techniques. At two weeks in the RCS retina, the RPE and retinal vessels, and their basal laminae, appeared normal. By two months, the RPE was hypertrophic and duplicated in some areas, and flattened in others. The RPE basal lamina was thickened (171% of the control, p less than .01), and there were more anionic sites along the RPE basal surface (158% of the control, p less than .01). Patches of displaced basal lamina material appeared within the RPE basal infoldings. By four months and later numerous retinal vessels were present within the RPE layer. In addition, cords of migrating RPE cells surrounded presumptive new vessels branching from the RPE layer towards the inner limiting membrane. The RPE-associated vessels exhibited diaphragmed fenestrae and channels, unlike normal retinal vessels, and their basal laminae were marked by anionic sites. These observations of RPE and extracellular matrix changes prior to vascular proliferation, and VRM formation in the dystrophic retina suggest that the RPE-associated extracellular matrix changes may contribute to vascular alterations in the dystrophic retina. A preliminary report of these findings has been presented previously.
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The relationship between microalbuminuria and retinal vessel responses to sustained handgrip contraction was studied in a group of 20 diabetic patients. The diabetics were divided into two groups based on their albumin excretion rates (AER): Group 1 (AER less than or equal to 10 mcg/min) consisted of ten diabetic patients, mean age 55.8 +/- 3.9 years (mean +/- SEM); five IDDM and five NIDDM. Group 2 (AER greater than 10 mcg/min) comprised ten diabetic patients: mean age 56.8 +/- 3.04 years; six IDDM and four NIDDM. Both groups were similar in that there were no significant differences between mean age, type of diabetes, mean duration of diabetes, glycaemic control or mean resting blood pressures. Group 2 diabetics had a higher incidence of autonomic dysfunction than Group 1, based on the results of four standard tests of autonomic nerve function. There were significantly decreased retinal vessel responses to sustained handgrip contraction in Group 2 diabetics (mean arteriolar constriction 0.1 +/- 0.32%, and mean venule constriction 1.0% +/- 0.99%) compared with Group 1 diabetics (mean arteriolar constriction 6.9 +/- 1.69%, and mean venule constriction 4.2 +/- 0.05%). Retinopathy was slightly worse in Group 2. The implications of the association of microalbuminuria (AER greater than 10 mcg/min) and loss of retinal vessel reactivity to sustained handgrip contraction are discussed.
A surgical technique was developed in pigs that permits access to the retinal venous plexus surrounding the optic nerve. The effect of surgery on ocular blood flow and capillary permeability was evaluated. Blood flow, determined by the labelled microsphere technique, did not differ significantly between operated and control eyes. Increased intraocular pressure in the operated eye reduced blood flow through the choroid and the anterior uvea in proportion to the reduction in perfusion pressure, while in the retina a smaller reduction in blood flow occurred indicating that autoregulatory mechanisms are involved in the control of retinal blood flow. The capillary permeability to sodium was studied by the single injection technique, using albumin as a reference substance. The fractional initial extractions from the choroidal and the retinal vessels were 0.77 and -0.001 respectively. The absence of a sodium extraction from the retinal vessel indicates that this part of the blood-retinal barrier was intact and that the blood drained by the retinal plexus is not mixed with blood from other sources.
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