Bruch's Membrane (bruch + membrane)

Distribution by Scientific Domains


Selected Abstracts


Fine Structure of the Retinal Pigment Epithelium, Bruch's Membrane and Choriocapillaris in the Horse

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2000
H. Altunay
Summary The fine structure of the retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris was investigated by light and transmission electron microscopy in both the tapetal and non-tapetal fundus of the horse eye. In all locations, the RPE consisted of a single layer of low cuboidal cells. The epithelial cells were joined laterally by apically located tight junctions. These cells displayed numerous basal infoldings and abundant thin apical processes which enclosed the rod outer segments. The epithelial cell nuclei were large and located basally. Within the epithelial cells, smooth endoplasmic reticulum was very abundant, while rough endoplasmic reticulum was scarce. polysomes and mitochondria, which often display a ring-shaped struccture, were abundant. Melanosomes were abundant in the non-tapetal area but absent in the tapetal area. Bruch's membrane was pentalaminate throughout the retina. The endothelium of the choriocapillaris was heavily fenestrated. [source]


Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001
Keisuke Mori
In this study, we investigated whether overexpression of pigment epithelium-derived factor (PEDF) by gene transfer can inhibit neovascularization by testing its effect in three different models of ocular neovascularization. Intravitreous injection of an adenoviral vector encoding PEDF resulted in expression of PEDF mRNA in the eye measured by RT-PCR and increased immunohistochemical staining for PEDF protein throughout the retina. In mice with laser-induced rupture of Bruch's membrane, choroidal neovascularization was significantly reduced after intravitreous injection of PEDF vector compared to injection of null vector or no injection. Subretinal injection of the PEDF vector resulted in prominent staining for PEDF in retinal pigmented epithelial cells and strong inhibition of choroidal neovascularization. In two models of retinal neovascularization (transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors and mice with oxygen-induced ischemic retinopathy), intravitreous injection of null vector resulted in decreased neovascularization compared to no injection, but intravitreous injection of PEDF vector resulted in further inhibition of neovascularization that was statistically significant. These data suggest that sustained increased intraocular expression of PEDF by gene therapy might provide a promising approach for treatment of ocular neovascularization. © 2001 Wiley-Liss, Inc. [source]


Optimized Architecture for Nutrition in the Avascular Retina of Megachiroptera

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2007
D. K. Brudenall
Summary Investigations were undertaken to evaluate the unique choroidal vascular system of the Megachiroptera (fruit bats) and its possible significance for retinal nutrition. Fluorescein angiography was performed and documented on Pteropus poliocephalus. Vascular casts were made of the eye of Pteropus scapulatus. Histologic evaluation was performed on P. scapulatus. Results confirmed that each papilla has a vascular core, and a unique vascular system emanating from the optic disc. The histological appearance of the choroid and retina of P. scapulatus confirmed a vascular core to the papillae with a thin, but definite Bruch's membrane. Megachiroptera have a unique vascular system to supply nutrition to the retina consisting of capillary loops within a dense, uniform mosaic of choroidal projections or papillae, which permit the diffusion of metabolites to the retina and a heretofore undescribed vascular tuft emanating from the optic disc. We suggest that this vascular system provides nutrition by diffusion to a thick avascular retina, without any shadowing by vessels, and allows for nocturnal visual acuity and light-gathering capabilities. [source]


Fine Structure of the Retinal Pigment Epithelium, Bruch's Membrane and Choriocapillaris in the Horse

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2000
H. Altunay
Summary The fine structure of the retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris was investigated by light and transmission electron microscopy in both the tapetal and non-tapetal fundus of the horse eye. In all locations, the RPE consisted of a single layer of low cuboidal cells. The epithelial cells were joined laterally by apically located tight junctions. These cells displayed numerous basal infoldings and abundant thin apical processes which enclosed the rod outer segments. The epithelial cell nuclei were large and located basally. Within the epithelial cells, smooth endoplasmic reticulum was very abundant, while rough endoplasmic reticulum was scarce. polysomes and mitochondria, which often display a ring-shaped struccture, were abundant. Melanosomes were abundant in the non-tapetal area but absent in the tapetal area. Bruch's membrane was pentalaminate throughout the retina. The endothelium of the choriocapillaris was heavily fenestrated. [source]


Pseudoxanthoma elasticum: biopsy of clinically normal skin in the investigation of patients with angioid streaks

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2007
S.J. Brown
Summary Background Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by fragmentation and calcification of elastic fibres with resultant pathological changes in the dermis, Bruch's membrane and blood vessels. Defects in Bruch's membrane produce angioid streaks on the retina but this appearance is not pathognomonic of PXE. Biopsy of clinically normal skin or scar tissue in patients with angioid streaks may show the histological features of PXE. Objectives To test the hypothesis that biopsy of clinically normal skin is a useful investigation in patients with angioid streaks. Methods This prospective study investigated 18 consecutive patients with angioid streaks. Each patient underwent a full dermatological examination and was investigated for diseases known to be associated with angioid streaks. Axillary skin biopsies were taken from 14 consenting patients. Results Typical PXE was found in 11 patients. No other diseases associated with angioid streaks were identified. Five patients had angioid streaks in the absence of systemic disease. Two patients had nondiagnostic dermatological features which were not clarified by histology. Two of the 11 patients with PXE showed histological evidence of PXE from clinically normal axillary skin. However, in both cases flexural skin elsewhere showed the typical clinical and histological features of PXE. Conclusions This study demonstrates the association between angioid streaks and PXE. However, it does not support the hypothesis that biopsy of normal-looking skin is helpful in the investigation of adult patients with angioid streaks. [source]


2231: Age-related modifications in RPE cells

ACTA OPHTHALMOLOGICA, Issue 2010
E MANNERMAA
Age-related macular degeneration (AMD) is a multi-factorial polygenetic aging disease. It has been shown that RPE dysfunction predisposes neural retinal dysfunction and the development of choroidal neovascularization. The pathogenesis of age-related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrades especially cellular proteins damaged by oxidative stress. The cross-talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD is discussed. In addition, age related changes in Bruch's membrane and choroidal blood flow may take part in the pathogenesis of AMD. This will be also discussed. [source]


Clinical and histological findings after intravitreal injection of bevacizumab (Avastin®) in a porcine model of choroidal neovascularization

ACTA OPHTHALMOLOGICA, Issue 3 2010
Nathan Lassota
Abstract. Purpose:, To examine the effect of intravitreally injected bevacizumab (Avastin®) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. Methods:, Choroidal neovascularization was induced surgically in 11 porcine eyes by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. Results:, Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes leaking on FA, whereas only one of five bevacizumab-injected eyes exhibited leakage. On histological examination, all 11 eyes contained CNV membranes of similar size, regardless of treatment. The number of vascular endothelial cells was significantly reduced (p = 0.03) in CNV membranes from eyes that had been injected with bevacizumab when compared with CNV membranes from placebo-injected eyes. There was a trend towards more retinal pigment epithelium cells (p = 0.16) and fewer glial fibres (p = 0.08) in membranes from bevacizumab-treated eyes compared with placebo-treated eyes. Bevacizumab was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. Conclusions:, Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection. [source]


Encouraging results of a VEGF kinoid against experimental choroidal neovascularization

ACTA OPHTHALMOLOGICA, Issue 2009
B ABITBOL
Purpose The goal of this preliminary study was to evaluate the preventive and curative antiangiogenic properties of a VEGF KINOID vaccine produced by NEOVACS againt experimentally laser induced murine choroidal neovessels Methods 3 groups of 12 adult mice (30g) were submitted to laser impacts breaking slightly the Bruch's membrane and initiating the development of subretinal choroidal neovessels. These laser impacts did not create immediately obvious choroidal lesions leading to blood hemorrhages.One Group of mice was submitted to repeated immunizations up to 5 immunizations by the VEGF Kinoid vaccine associated to a modified freund's adjuvant solution. One group of mice received only the mofified Freund's adjuvant and one group of mice sham injections of PBS in the same conditions. Results We were able to observe a decrease or even the disappearance of the abnormal choroidal neovessels even in animals that had been immunized but had not reached adequate levels of neutralizing antibodies against VEGF. Transient adverse effects were observed in some mice in all the groups of mice. Conclusion Obviously The modified freund's adjuvant solution utilized in this first set of experiments must be avoided or modified in order to avoid adverse effects. The chemistry for the production of the VEGF kinoid production must be improved in order to obtain a better immunizing vaccine. Commercial interest [source]


The AMD-associated complement factor H (CFH) polymorphism Y402H results in decreased CFH localisation to Bruch's membrane

ACTA OPHTHALMOLOGICA, Issue 2009
PN BISHOP
Purpose CFH down-regulates the alternative pathway of the complement system by binding to polyanionic structures on host cells/tissues and inactivating surface associated C3b. Recently, the Y402H polymorphism in CFH has been shown to be a major risk factor for AMD. Here we investigated the functional consequences of the Y402H polymorphism by testing the hypothesis that the resultant amino acid substitution alters CFH binding to macular tissue Methods The 402H and 402Y forms of full-length CFH and recombinant CFH fragments (composed of CCP6-8) were labelled with different fluorophores (402Y with AlexFluor-488 and 402H with AlexaFluor-594). These were simultaneously incubated with frozen sections of human macular tissue from donor eyes and the relative binding of the two forms was investigated. In some experiments the tissue sections were digested with glycosidic enzymes prior to incubation with the fluorescently-labelled proteins. Results Whilst the 402H and 402Y variants showed similar levels of binding to the RPE, there was a marked reduction in binding of the 402H form to Bruch's membrane. The binding of both forms to Bruch's membrane was dependent upon interactions with heparan sulfates, and to a lesser extent dermatan sulfates. Conclusion Complement mediated damage is important in the pathogenesis of AMD and the relative failure of the 402H form of CFH to localise to Bruch's membrane may result in over activation of the complement system at the retinal pigment epithelium/Bruch's membrane interface. [source]


Clinical and Histological Aspects of CNV Formation: Studies in an Animal Model

ACTA OPHTHALMOLOGICA, Issue thesis2 2008
Nathan Lassota MD
Abstract. The purpose of the present thesis was to develop an animal model of CNV in order to study the early formation of CNV and to test the effects of an anti-angiogenic treatment. Porcine eyes were chosen as a substrate for CNV induction, since they are similar to human eyes in terms of both macroscopic and microscopic morphology. However, a major difference is that pigs lack a fovea; instead they have a visual streak, with a relatively stable and high concentration of cones. By surgical perforation of Bruch's membrane we were able to induce formation of CNV membranes. The morphology and cellular composition of these membranes varied with the surgical technique employed. When RPE cells were locally removed at the time of perforation, the resulting CNV was thinner, contained fewer blood vessels and was less prone to leak on fluorescein angiography than when RPE cells were left intact at induction. The neuroretina overlying the perforation site was not damaged by any of the surgical techniques, thus allowing the subsequent retinal damage to be ascribed to the actual process of CNV formation. Using this animal model allowed us to directly map histological findings onto fluorescein angiograms and thereby perform meaningful correlations between histopathologic and photographic features. Such correlations have been hampered in human subjects, since human eyes are not enucleated as a consequence of CNV and are therefore only available for post-mortem studies. In such studies there often is a considerable time-gap between the death of the patient and the latest available fluorescein angiogram, thereby allowing macular pathology to evolve in the interim. Histological examination of the porcine membranes demonstrated that they were composed of RPE cells, glial cells, macrophages, endothelial cells, collagen and smooth muscle fibres, which are the same cellular and fibrillar elements that dominate human CNV membranes. The porcine model was applied to test the effects, in a randomized and masked fashion, of intravitreally injected bevacizumab. Bevacizumab, a pan VEGF A antibody, was found to reduce both the proliferation of endothelial cells in CNV membranes and the propensity to leak in fluorescein angiograms. Immunohistochemically, bevacizumab was detected in the inner limiting membrane, in retinal blood vessels and binding uniformly to the entire CNV membrane without any cellular predisposition. Based on the above findings we believe that the porcine CNV model shows a bearing to human disease and therefore might be used as a tool to obtain improved treatments for this debilitating condition. [source]


Inflammation in AMD pathology

ACTA OPHTHALMOLOGICA, Issue 2008
JZ NOWAK
Age-related macular degeneration (AMD) is a progressive retinal disease that leads to substantial irreversible vision loss in elderly patients. Two clinical categories of AMD are distinguished: the "dry" atrophic form and the exudative neovascular or "wet" form. There is neither a preventive therapy nor a cure for both forms, although recent efforts succeeded in a more effective treatment of the wet AMD with PDT and anti-VEGF drugs. AMD is a multifactorial pathology which involves complex interaction of metabolic, genetic and environmental factors, with major biochemical-clinical abnormalities seen in four functionally interrelated tissues: photoreceptors, retinal pigment epithelium, Bruch's membrane and choriocapilaries. Four processes specifically contribute to the development of AMD pathology: lipofuscinogenesis (in RPE cells), drusogenesis (with drusen located between RPE and Bruch's membrane), inflammation (local) and choroidal neovascularization (in wet form). Although the role of immune system and inflammation has been implicated in AMD pathogenesis for many years, an impetus to intensify the research in this direction gave a recent discovery of polymorphisms in genes that encode for elements of the complement system, including factor H (CFH; Y402H), factor B, and complement component 2. An increased activity of the complement alternative pathway due to the lack of or insufficient control by CFH appears to contribute to AMD progression via immunologic mechanism which drives inflammatory response. An arising question is whether blockade of overactive complement system will be a therapeutic strategy safe for patients and effective to prevent or slowing down the macula-devastating and vision-threatening disease. Supported by grant no. 503-1023-1 from Medical University of Lodz. [source]


Complement factor H and factor B expression in RPE cells

ACTA OPHTHALMOLOGICA, Issue 2008

Purpose Age-related macular degeneration (AMD) is the leading cause of untreatable blindness in the developed world. The pathogenesis of AMD is not fully understood. Recent evidence suggests that local inflammation in particular complement activation plays an important role. We aim to understand how complement activation is regulated at retina/choroidal interface. Methods The expression and distribution of complement factor H (CFH) and factor B (CFB) in mouse ocular tissues were examined by immunohistochemistry. Regulation of CFH and CFB gene expression by various cytokines or photoreceptor outer segments (POS) was investigated in vitro in cultured RPE cells. Changes in CFH or CFB gene expression after treatment were evaluated by RT-PCR. Results In normal mouse eyes, CFH was detected in corneal epithelial cells, ciliary body, RPE cells, Bruch's membrane and choroidal vessels. There is no significant change in either the expression level or the distribution pattern of CFH in ocular tissues of different ages of mice. CFB was exclusively detected in RPE cells in normal mice. The expression of CFB in RPE cells increases with age. In vitro in RPE cultures, the expression of CFH was negatively regulated by cytokine TNF-alpha and IL-6, whereas the expression of CFB was positively regulated by TNF-alpha and IFN-gamma. Short-term incubation of RPE cells with POS did not alter the expression of CFH or CFB, whereas long-term incubation of RPE cells with POS significantly down-regulated CFH expression but up-regulated CFB expression. Conclusion Complement regulatory factors CFH and CFB are produced locally in the retina/choroidal interface by RPE cells. The production of CFH and CFB in RPE cells is regulated differently by various cytokines and oxidized POS. [source]


Bruch's membrane and the vascular intima: is there a common basis for age-related changes and disease?

CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2005
Sobha Sivaprasad FRCS
Abstract Several clinical and epidemiological studies have concurrently illuminated established cardiovascular risk factors in age-related macular degeneration (AMD), raising the possibility that cardiovascular disease and AMD may share a similar pathogenic process. The vascular intima and the Bruch's membrane share several age-related changes and are the seat of many common molecules. Diseases of these structures may represent parallel responses to the tissue injury induced by multiple intercalated factors such as genetic variations, oxidative stress, inappropriately directed immune response or inflammatory disease complex. However, there are marked differences in the age-related changes in these two structures. The strategic location of the Bruch's membrane between the retinal pigment epithelium and the choriocapillaris can at least partially explain the differential susceptibility of AMD to cardiovascular risk factors. Unlike the vascular wall that is exposed to changes from the endothelium, the Bruch's membrane is subject to changes from both the endothelium (choriocapillaris) and epithelium (retinal pigment epithelium). Moreover, although both the vascular wall and Bruch's membrane become lipid laden with age, the lipid composition is characteristically different. This review examines the morphological and biochemical alterations in the senescent Bruch's membrane and its analogy to the vascular wall to evaluate the concurrence of atherosclerosis and AMD. [source]