Disease relevance of Bruch Membrane

• This is a macular degeneration disorder with characteristic ECM irregularities in Bruch's membrane [1].
• Thus, abnormal local function of TIMP-3 may lead to the characteristic Bruch's membrane deposits and choroidal neovascularization found in Sorsby's fundus dystrophy [2].
• Preretinal hemorrhages were created in rabbits by perforating Bruch's membrane with a high intensity krypton burn [3].
• In addition to the angioid streaks, the fundal findings in the probands affected included changes of the retinal pigment epithelium, exudative maculopathy, optic disc drusen and 'fire-work'-pattern of drusen of the Bruch's membrane [4].

High impact information on Bruch Membrane

• As shown by light and electron microscopy Abcc6-/- mice spontaneously developed calcification of elastic fibres in blood vessel walls and in Bruch's membrane in the eye [5].
• Drusen form within Bruch's membrane, a stratified extracellular matrix situated between the retinal pigmented epithelium and choriocapillaris [6].
• Our results were supported by significant accumulation and expression overlap of both TIMP-3 and EFEMP1 between the retinal pigment epithelia and Bruch membrane in the eyes of ML and AMD patients [7].
• Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant [8].
• Intravitreous or periocular injection of an adenoviral vector encoding sFlt-1 (AdsFlt-1.10) markedly suppressed choroidal neovascularization at rupture sites in Bruch's membrane [9].

Chemical compound and disease context of Bruch Membrane

• Prolonged choroidal filling on fluorescein angiography in age-related macular degeneration is thought to indicate diffuse thickening of Bruch's membrane [10].

Biological context of Bruch Membrane

• CONCLUSIONS: These findings indicate relationships between higher pulse pressure (a presumed indicator of age-related elastin and collagen changes in Bruch's membrane) and systolic blood pressure with an increased 10-year incidence of some lesions defining early age-related maculopathy and exudative macular degeneration [11].
• TIMP-3 bound to collagen VI may be more resistant to degradation and create an imbalance between the normal amount of TIMP-3 and matrix metalloproteinases (the substrate of TIMPs) in Bruch's membrane with consequent disruption of the normal metabolic processes [12].
• RT-qPCR showed significant upregulation of RAGE, AGE R1, and AGE R3 in RPE cells overlying basal deposits compared to cells attached to morphologically normal Bruch's membrane [13].
• We investigated the effects of age-related changes within the Bruch membrane on the gene expression profile of the RPE [14].
• Effects of extracellular matrix and Bruch's membrane on retinal outer segment phagocytosis by cultured human retinal pigment epithelium [15].

Anatomical context of Bruch Membrane

• The major phospholipid classes in retina, retinal pigment epithelium, and Bruch's membrane/choroid were phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, and phosphatidyl serine; the major fatty acids were palmitic (16:0), stearic (18:0), and oleic (18:1) [16].
• Two monoclonal antibodies (Mab 4D5 and 2D6) raised against the core protein of a basement membrane chondroitin sulfate proteoglycan from Reichert's membrane of the rat, were used for ultrastructural immunoperoxidase localization of this protein in Bruch's membrane of the rat [17].
• RESULTS: Birefringent anisotropic droplets ("maltese crosses") with melting characteristics of cholesterol esters were identified within diffuse Bruch's membrane deposits, drusen, and sclera [18].
• The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane [19].
• After yellow light exposures of < 3700 J/cm2 and in rabbits with no significant fluorescein leakage, the HRP was limited to the choroidal capillaries and Bruch's membrane [20].

Associations of Bruch Membrane with chemical compounds

• Sixty percent of total cholesterol was esterified, and Bruch's membrane EC was 16- to 40-fold enriched relative to plasma [21].
• Ultrastructural immunocytochemical localization of chondroitin sulfate proteoglycan in Bruch's membrane of the rat [17].
• CONCLUSIONS: These findings suggest that this complement regulatory protein, which protects host cells from autologous complement attack, may have a functional interaction with beta1 integrin in the eye that is related to RPE adhesion to its basement membrane and Bruch's membrane [22].
• One month after iodate, patches of Bruch's membrane were devoid of RPE, which was replaced by scar tissue [23].
• Increase in the advanced glycation end product pentosidine in Bruch's membrane with age [24].

Gene context of Bruch Membrane

• Tissue-type PA (t-PA) was found in endothelium of blood vessels and in tumour cells in almost all lesions, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour-related death could be established [25].
• PURPOSE: Mutations in the gene encoding the tissue inhibitor of metalloproteinases-3 (TIMP3) have been shown previously to cause Sorsby's fundus dystrophy, an autosomal-dominant disorder characterized by extracellular matrix irregularities in Bruch's membrane [26].
• MMP-9 was distributed evenly in Bruch's membrane with some patchy presence in the choroidal mass [27].
• The localization of the mutant protein in the eye is normal, although there is evidence of increased Timp3 levels in Bruch's membrane of mutant animals [28].
• MMP-1 and -3 were localized primarily to Bruch's membrane [27].

Analytical, diagnostic and therapeutic context of Bruch Membrane

• Frozen sections of eye bank eyes showed antigen specific staining for collagen types I, III, and IV, and for fibronectin and laminin in Bruch's membrane and surrounding the RPE [29].
• 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 [30].
• Human retinal epithelial cells dividing in culture have been radiolabelled with tritiated thymidine and subsequently transplanted and identified on Bruch's membrane of owl monkey by autoradiography [31].
• Immunohistochemistry of human retina/choroid sections shows pronounced TIMP-3 immunostaining in Bruch's membrane, particularly near the surface of the RPE and endothelial cells, presumably in their basement membranes, with minimal staining in other portions of the retina [32].
• 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 [14].

References