Bruch's membrane changes in transgenic mice overexpressing the human biglycan and apolipoprotein b-100 genes

Ferenc B. Sallo, Erika Bereczki, T. Csont, Philip J. Luthert, Peter Munro, P. Ferdinándy, M. Sántha, Imre Lengyel

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Age-Related Macular Degeneration (AMD) is characterized by the accumulation of lipid- and protein-rich deposits in Bruch's Membrane (BrM). A consequent decrease in hydraulic conductivity and impairment of transport through BrM may play a central role in the pathogenesis of AMD. The mechanism of deposit formation in AMD had been suggested to show similarities to the formation of atherosclerotic plaques in which the interactions of extracellular matrix proteoglycans with apolipoprotein-B 100 (apoB-100) play an important role. A prime candidate for this interaction is the small leucin-rich proteoglycan biglycan. The aim of our study was to test the effect of the simultaneous overexpression of human apoB-100 and biglycan genes in combination with a high-cholesterol diet on BrM morphology in transgenic mice. Six-weeks-old homozygous apoB-100 or biglycan, hemizygous apoB-100/biglycan transgenic and wild-type C57Bl/6 mice were fed either a standard chow or a diet supplemented with 2% cholesterol for 17 weeks. Animals were sacrificed, serum lipid levels were measured and eyes were processed for transmission electron microscopy (TEM) according to standard protocol. Morphometric analysis of digitally acquired TEM images of BrM showed that in apoB-100 and double transgenic animals fed a high-cholesterol diet, the BrM thickness was significantly increased compared to wild-type animals. Both groups had electron-lucent profiles in clusters, scattered throughout the collagenous layers of BrM, and focal nodules of an amorphous material of intermediate electron-density between the plasma and basement membranes of the retinal pigment epithelium (RPE). BrM thickness in these two groups correlated well with elevated cholesterol levels. Unexpectedly, animals overexpressing biglycan alone showed a marked, diet-independent increase in BrM thickness associated with a layer of a basement membrane-like material in outer BrM. The effects of biglycan overexpression are intriguing and further investigations are needed to elucidate the underlying mechanisms. Crown

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalExperimental Eye Research
Volume89
Issue number2
DOIs
Publication statusPublished - Aug 2009

Fingerprint

Biglycan
Bruch Membrane
Apolipoproteins
Transgenic Mice
Apolipoprotein B-100
Genes
Macular Degeneration
Diet
Cholesterol
Proteoglycans
Transmission Electron Microscopy
Basement Membrane
Electrons
Lipids
Genetically Modified Animals
Wild Animals
Retinal Pigment Epithelium
Atherosclerotic Plaques
Hypercholesterolemia
Crowns

Keywords

  • age-related macular degeneration
  • Bruch's membrane
  • electron microscopy
  • lipids
  • lipoproteins
  • pigment epithelium of the eye
  • proteoglycans
  • retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Bruch's membrane changes in transgenic mice overexpressing the human biglycan and apolipoprotein b-100 genes. / Sallo, Ferenc B.; Bereczki, Erika; Csont, T.; Luthert, Philip J.; Munro, Peter; Ferdinándy, P.; Sántha, M.; Lengyel, Imre.

In: Experimental Eye Research, Vol. 89, No. 2, 08.2009, p. 178-186.

Research output: Contribution to journalArticle

Sallo, Ferenc B. ; Bereczki, Erika ; Csont, T. ; Luthert, Philip J. ; Munro, Peter ; Ferdinándy, P. ; Sántha, M. ; Lengyel, Imre. / Bruch's membrane changes in transgenic mice overexpressing the human biglycan and apolipoprotein b-100 genes. In: Experimental Eye Research. 2009 ; Vol. 89, No. 2. pp. 178-186.
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abstract = "Age-Related Macular Degeneration (AMD) is characterized by the accumulation of lipid- and protein-rich deposits in Bruch's Membrane (BrM). A consequent decrease in hydraulic conductivity and impairment of transport through BrM may play a central role in the pathogenesis of AMD. The mechanism of deposit formation in AMD had been suggested to show similarities to the formation of atherosclerotic plaques in which the interactions of extracellular matrix proteoglycans with apolipoprotein-B 100 (apoB-100) play an important role. A prime candidate for this interaction is the small leucin-rich proteoglycan biglycan. The aim of our study was to test the effect of the simultaneous overexpression of human apoB-100 and biglycan genes in combination with a high-cholesterol diet on BrM morphology in transgenic mice. Six-weeks-old homozygous apoB-100 or biglycan, hemizygous apoB-100/biglycan transgenic and wild-type C57Bl/6 mice were fed either a standard chow or a diet supplemented with 2{\%} cholesterol for 17 weeks. Animals were sacrificed, serum lipid levels were measured and eyes were processed for transmission electron microscopy (TEM) according to standard protocol. Morphometric analysis of digitally acquired TEM images of BrM showed that in apoB-100 and double transgenic animals fed a high-cholesterol diet, the BrM thickness was significantly increased compared to wild-type animals. Both groups had electron-lucent profiles in clusters, scattered throughout the collagenous layers of BrM, and focal nodules of an amorphous material of intermediate electron-density between the plasma and basement membranes of the retinal pigment epithelium (RPE). BrM thickness in these two groups correlated well with elevated cholesterol levels. Unexpectedly, animals overexpressing biglycan alone showed a marked, diet-independent increase in BrM thickness associated with a layer of a basement membrane-like material in outer BrM. The effects of biglycan overexpression are intriguing and further investigations are needed to elucidate the underlying mechanisms. Crown",
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