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At least 19 recordsLinked to original sources
PubMed2001

Murine high-fat diet and laser photochemical model of basal deposits in Bruch membrane.

OBJECTIVE: To examine the histologic, histochemical, and ultrastructural changes in Bruch membrane in mice on a high-fat diet with and without laser photochemical injury. METHODS: Five groups of C57BL/6 mice were studied. Group 1 included 2-month-old mice on a normal diet; group 2 included 8-month-old mice on a normal diet; group 3 included 8-month-old mice on a high-fat diet; groups 4 and 5 included 8-month-old mice on a normal diet or high-fat diet, respectively, that underwent laser application of one eye with argon blue laser (488 nm). The mice were killed and plasma lipid levels were measured. The eyes were examined by standard electron microscopy, filipin histochemistry for unesterified cholesterol (UC) and esterified cholesterol (EC), and the osmium-tannic acid-phenylenediamine method for preserving extracellular lipid particles. RESULTS: The plasma cholesterol level was significantly higher in the mice on the high-fat diet than the controls (P<.001). Bruch membrane was thicker in group 2 than group 1 (P =.04) and group 3 had a thicker Bruch membrane than group 2 (P =.003). All eyes in group 3 exhibited accumulation of electron-lucent debris. There was no histochemical and ultrastructural evidence that this material represented accumulated UC or EC. Seven of 9 laser-injured eyes in group 5 accumulated basal laminar deposit (BlamD)-like material in Bruch membrane (P =.02). CONCLUSIONS: Electron-lucent debris accumulates in murine Bruch membrane, and the amount correlates with age and high-fat diet. This debris has some similarities with basal linear deposits, although the debris does not form a discrete layer external to the basement membrane of the retinal pigment epithelium as occurs in basal linear deposits. These deposits do not appear to be UC or EC. Laser photochemical injury of the retinal pigment epithelium may result in the appearance of BlamD-like deposits in eyes with electron-lucent debris. The BlamD-like deposits in this model are similar to the basal laminar deposits that occur in age-related macular degeneration. CLINICAL RELEVANCE: This is an animal model of ultrastructural BlamD-like material in Bruch membrane that is very similar to the deposits that occur in age-related macular degeneration.

Animals↗
PubMed2006

Bruch membrane aging alters the gene expression profile of human retinal pigment epithelium.

We investigated the effects of age-related changes within the Bruch membrane on the gene expression profile of the RPE. Immortalized human ARPE-19 cells were seeded onto acellular human Bruch membrane from younger and older donors and harvested 72 hr later; total RNA was isolated and the gene expression profile was determined using the Affymetrix Human Genome U95A gene chip. Twelve genes were upregulated and 8 genes were downregulated with Bruch membrane aging; RT-PCR confirms that Bruch membrane aging upregulates genes in RPE cells encoding for transforming growth factor alpha and downregulates genes for vitronectin and the membrane transporter ABCC5. The role of these changes in the pathogenesis of age-related diseases such as macular degeneration remains to be elucidated.

Adult↗
PubMed2001

Metastatic adenocarcinoma with rupture through the Bruch membrane simulating a choroidal melanoma.

PURPOSE: To report a case of adenocarcinoma metastatic to the choroid with rupture through the Bruch membrane, thus, simulating a choroidal melanoma. METHODS: Interventional case report. Evaluation in a university-based clinic, including a complete eye examination, fluorescein angiography, and ultrasonography; oncological evaluation; and eventual enucleation with histopathological study, including immunohistochemical stains. RESULTS: A 62-year-old Hispanic female presented with visual loss, right eye, of short duration because of a choroidal mass with retinal detachment. Ultrasonography showed a dome-shaped lesion with an eccentric collar-button projection and medium internal reflectivity, which suggested a choroidal melanoma. Initial systemic evaluation was negative. Severe pain necessitated enucleation, RE, and histopathology of the choroidal mass demonstrated an adenocarcinoma. Further examination revealed a left, upper lobe, nonsmall cell lung carcinoma. CONCLUSION: Metastatic choroidal tumors may present, although rarely, with collar-button configurations.

Adenocarcinoma↗
PubMed1992

[The Bruch membrane and choroid. Angiography and functional characteristics in age-related changes].

Age-related changes in the retinal pigment epithelium and Bruch's membrane are believed to play an important role in the pathogenesis of age-related macular degeneration. Ophthalmoscopically visible drusen in the macular area may precede the complications causing visual loss. In addition to these localized depositions of debris in Bruch's membrane, histological methods could demonstrate linear deposits in Bruch's membrane which may also profoundly influence the development of complicated macular aging changes. It is difficult to identify linear deposits clinically, but as an indirect criterion for diffuse thickening and linear deposits in Bruch's membrane regression of the choriocapillaris with consequent prolongation of the choroidal filling phase in fluorescein angiography is suggested. This feature was observed in 26% of elderly patient. In association with these areas of regressed choroidal capillaries, loss of visual function was found in fine matrix perimetry.

Aged↗
PubMed2000

[Adhesive properties of basal membranes of Bruch's membrane. Immunohistochemical studies of age-dependent changes in adhesive molecules and lipid deposits].

BACKGROUND: In addition to deposition of debris between the plasma and basal membrane of the RPE, different types of early and late AMD-like drusen, choroidal neovascularization and pigment epithelial detachments are characterized by splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer. Because these layers are normally attached by adhesion molecules, the possible age-related regression of these adhesion molecules in this structure was examined. METHODS: The presence of the adhesion molecules laminin, fibronectin, collagen IV and of lipid deposits was examined in 44 macular specimen (age 4-88 years). RESULTS: Age-related regression of the adhesion molecules laminin, fibronectin and collagen IV was observed in the basement membrane of the RPE and the endothelium cells of the choriocapillaris. This effect correlated with an increase in lipid deposits. CONCLUSION: The regression of adhesion molecules, especially in the basement membrane of the RPE in association with increased lipid deposits in Bruch's membrane, may explain the development of a "cleavage edge" for the splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer.

Adolescent↗
PubMedDate not supplied

Age-related antioxidant capacity of the vitreous and its possible relationship with simultaneous changes in photoreceptors, retinal pigment epithelium and Bruchs' membrane in human donors' eyes.

It is well established that the retina undergoes several decremental functional and structural changes with age, and it has been suggested that most of these age-related changes may be mainly due to oxidative stress through light-induced mechanisms. While the cornea and the lens absorb part of the light radiation, the vitreous appears to be the main site of protection against radiation damage to the retina. Thus the purpose of this study was to explore possible interrelationships between the oxidative capacity of the vitreous and the number of photoreceptors, the fluorescent intensity of the retina, and the thickness of the Bruch's membrane in eyes from donors dying from the third to the eighth decade of life. The results showed that the total reactive antioxidant potential of the vitreous significantly decreased with the age of the donor's eyes, and that this decrease was directly correlated with decreases in the photoreceptors and inversely correlated with increases in the autofluorescent intensity of the retina and the thickness of the Bruch's membrane. Although these correlations did not prove a cause-effect relationship, these findings may provide new insights for the understanding and possible treatment of the age-dependent changes of the human eyes.

Journal Article↗
PubMed1989

Analysis of newly synthesized Bruch's membrane proteoglycans.

Bruch's membrane may provide a selective filtration barrier for nutrients coming from the choriocapillaris to the outer retina. Because proteoglycans have been shown to have structural and filtration properties in other tissues, we have been investigating the deposition of newly synthesized proteoglycans into Bruch's membrane and how these may be affected by aging and pathology. Proteoglycans deposited in human Bruch's membrane were metabolically labelled with 35SO4 and 3H-glucosamine using a whole-eye organ culture system. Labeled proteoglycans were extracted from dissected Bruch's membranes with 4 M guanidine and isolated by ion-exchange column chromatography on DEAE cellulose using a linear salt gradient. These molecules were subsequently chromatographed on Sepharose CL-4B and glycosaminoglycan content characterized by enzymatic and chemical degradation. The elution profiles for proteoglycans remains relatively unchanged with age, although in eyes from donors over age 70 there is a small change in size distribution toward higher molecular weights. However, the proportions of newly synthesized glycosaminoglycans remain unchanged with age, being approximately 75% chondroitin sulfate/dermatan sulfate and 25% heparan sulfate. Bruch's membrane proteoglycans from donors with different retinal pathologies, however, exhibited an increased proportion of heparan sulfate. Considering the structural and filtration properties of proteoglycans, such alterations could result in abnormal functioning of Bruch's membrane that could ultimately affect the maintenance of the outer retina.

Adult↗
PubMed2005

Study of the morphological and adhesion properties of collagen fibers in the Bruch's membrane.

The Bruch's membrane is located beneath the retina in vertebrate eyes. We have used atomic force microscopy to examine the morphological and adhesion properties of collagen fibers located in different portions of the membrane. The D-periodicity of the fibers was 62.54 +/- 4.25 nm and 63.78 +/- 4.14 nm for regions away from the optic nerve and close to it, respectively. The adhesion properties of the collagen fibers were evaluated using force volume imaging on a number of different eye samples. The adhesion force we recorded in regions away from the optic nerve was different compared to regions close to the optic nerve. The reported results allow us to understand the nanoscopic properties of connective tissues in the eye and are important for the design of new and improved biomaterials.

Animals↗
PubMed1986

Ultrastructure of Bruch's membrane after krypton laser photocoagulation. I. Breakdown of Bruch's membrane.

Previous observations on rats suggested that subretinal neovascularization does not require a prior break in Bruch's membrane (BM). We verified this observation by using scanning electron microscopy to examine large expanses of BM that became exposed following ophthalmoscopically white krypton laser burns. Bruch's membrane appeared intact in the acute phase after injury. Subsequently, slitlike defects in BM were associated with penetrating choroidal capillaries. These observations were consistent with transmission electron microscopic findings of cellular protrusions arising from the choriocapillary endothelial cells and from regenerating retinal pigment epithelial (RPE) cells invading BM. These cell-formed defects in BM differed from thermal defects in appearance, size, and onset of occurrence. Endothelial cells penetrated all layers of BM, including the RPE basement membrane. We conclude that endothelial cells can erode their own basement membrane and the RPE basement membrane, and krypton laser burns with or without immediate rupture of BM induce cellular activity that may result in defects in BM.

Animals↗
PubMed1986

Ultrastructure of Bruch's membrane after krypton laser photocoagulation. II. Repair of Bruch's membrane and the role of macrophages.

The accompanying ultrastructural study showed that ophthalmoscopically white krypton laser photocoagulation in rats is followed by cellular invasion causing breakdown of Bruch's membrane (BM). We have expanded these observations, using scanning electron microscopy, transmission electron microscopy, and high-voltage transmission electron microscopy to describe the healing process. The repair of BM involves regenerating retinal pigment epithelial cells and choriocapillaris (CC) that form new basement membranes and fibroblasts that secrete collagen and elastin. The reformation of the CC is also associated with subretinal neovascularization. The involvement of macrophages was evident throughout the process of BM repair and formation of new vessels. We propose that the macrophages act as a common factor linking the diverse diseases associated with choroidal subretinal neovascularization, deduced from our evaluation of the healing process and the reformation of choriocapillaris.

Animals↗
PubMed1994

Analysis of lipid deposits extracted from human macular and peripheral Bruch's membrane.

OBJECTIVE: Lipids in Bruch's membrane may affect the evolution of age-related macular disease. To determine whether these show differences in regional distribution, we analyzed lipid deposits in Bruch's membrane at macular and peripheral sites. METHODS: Thin-layer chromatography was used to measure different lipid classes extracted from macular and peripheral Bruch's membrane of 32 eye bank eyes. RESULTS: The quantity of lipid extracted was consistently higher in the macula than in the periphery of human eyes. The total from both sites and the difference between the sites increased with age. The extracted lipids consisted largely of phospholipids, triglycerides, fatty acids, and free cholesterol. There was little cholesterol ester. CONCLUSIONS: Accumulation of lipids with age appears to be greater in the central than in the peripheral region of the fundus, indicating that lesions in age-related macular degeneration and Bruch's membrane lipid deposits share a common spatial distribution. The composition is consistent with the lipids being of cellular origin.

Adolescent↗
PubMed2005

Impaired RPE survival on aged submacular human Bruch's membrane.

Resurfacing of diseased or iatrogenically damaged Bruch's membrane with healthy retinal pigment epithelium (RPE) has been proposed as adjunctive treatment for age-related macular degeneration (AMD). The purpose of this study was to determine whether cultured fetal human RPE cells can attach and differentiate on aged submacular human Bruch's membrane. Bruch's membrane was debrided to expose native RPE basement membrane, the superficial inner collagenous layer directly below the RPE basement membrane, or the deep inner collagenous layer. These are three surfaces that transplanted RPE cells will encounter in situ. Approximately 3146 cultured fetal RPE cells mm(-2) were seeded onto these three surfaces and grown in organ culture for 1, 7, or 14 days. Explants were bisected and examined histologically or analyzed with a scanning electron microscope. RPE nuclear density was measured on stained sections. Morphology and cell density were compared to cells seeded onto bovine corneal endothelial cell-extracellular matrix (BCE-ECM). In situ submacular RPE nuclear density was also measured in tissue sections of donor eyes ranging from 18 weeks gestation to 88 years of age to determine the effect of age on RPE density. Compared to cells seeded onto BCE-ECM at similar density, RPE cell coverage and cellular morphology on aged submacular human Bruch's membrane was poor at all time points. In contrast to cells on BCE-ECM, RPE cell density on Bruch's membrane decreased with time. In general, cell morphology on all three Bruch's membrane surfaces worsened by day-7 compared to day-1. Although some cells were more pigmented on RPE basement membrane and the deep inner collagenous layer at day-7, poor cellular morphology indicated the remaining cells were not well differentiated. At day-14, the cells were uniform and cuboidal on BCE-ECM, with cell density similar to that at day-7 and similar to in situ density of young donors (<age 30 years). The morphology of cells on Bruch's membrane was variable, and the nuclear density declined over time. A Bruch's membrane explant from a donor with large soft drusen showed the poorest resurfacing at day-7 in organ culture. These data indicate that aged submacular human Bruch's membrane does not support transplanted RPE survival and differentiation readily. The formation of localized RPE defects, cell death, and worsening cellular morphology on aged Bruch's membrane indicates that modification of Bruch's membrane may be necessary to prevent graft failure in AMD patients receiving RPE transplants.

Adolescent↗
PubMed1985

Altered synthesis of Bruch's membrane proteoglycans associated with dominant retinitis pigmentosa.

Proteoglycans, extracellular matrix molecules that have been shown to have filtration properties in some tissues, make up a significant proportion of the structural macromolecules of Bruch's membrane. Bruch's membrane may provide a selective filtration barrier between the choriocapillaris and the pigmented epithelium (PE) and outer retina. In this paper, we compare the proteoglycans extracted from metabolically-labeled normal and retinitis pigmentosa (RP) Bruch's membranes. Isolated RP Bruch's membrane proteoglycans were larger than those from normal donor eyes when chromatographed on a column of Sepharose CL-4B. In addition to the increased size, there was also a dramatic increase in the proportion of heparan sulfate proteoglycan being synthesized in RP. Considering the structural and filtration properties of proteoglycans, alterations such as these could affect the functioning of Bruch's membrane and, possibly, the PE and the outer retina.

Chondroitin Sulfates↗
PubMed2003

Bruch's membrane of the brachymorphic mouse.

Bruch's membrane exists between the retinal pigment epithelium and the choriocapillary endothelium. Its structure is very complicated, having five sublayers containing basement membranes of retinal pigment epithelium and choriocapillary endothelium, outer and inner collagenous layers, and a central elastic layer. In the development of Bruch's membrane in normal mice, both basement membranes are created first. Secondarily, collagen fibers are accumulated in the space between these basement membranes and then form a collagenous layer. Finally, the elastic layer elaborated in the collagenous layer separates this into outer and inner collagenous layers. Brachymorphic mice have a disorder in the sulfation pathway, resulting in undersulfation. Consequently, in Bruch's membrane of brachymorphic mice, the expression of decorin, a small proteoglycan containing chondroitin sulfate and an indispensable component in collagen assembly, is at a very low level. It is clear that hypoplasia of the collagenous layer in Bruch's membrane of brachymorphic mice induces a disorder in the following formation of the elastic layer. These findings suggest that the formation of the collagenous layer, regulated with acidic glycoconjugates such as decorin, is important in the development of Bruch's membrane.

Animals↗
PubMed1983

Biosynthesis of proteoglycans present in primate Bruch's membrane.

The proteoglycan components of Bruch's membrane have not been well characterized to date. In this study, the glycosaminoglycans present in Bruch's membrane were identified and found to be heparan sulfate with small amounts of chondroitin and/or dermatan sulfate and hyaluronic acid. The biosynthesis of glycosaminoglycans and their incorporation into proteoglycans was investigated using an eye organ culture in which the cornea, iris, and sclera had been removed. The newly synthesized proteoglycan(s) extracted with 4 M guanidine hydrochloride bound to a DEAE-cellulose column and eluted with approximately 0.44 M NaCl. The proteoglycan(s) had a molecular weight ranging from 100,000 to 150,000 daltons. After papain treatment, the glycosaminoglycan side chains had a molecular weight of approximately 44,000 daltons. The newly synthesized proteoglycan(s) contained 65% chondroitin and/or dermatan sulfate and 35% heparan sulfate. This organ culture system should be useful in studying disease states of Bruch's membrane.

Animals↗