Plasma apolipoproteins and risk for age related maculopathy

Dashti, Nassrin; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A.

doi:10.1136/bjo.2006.093856

Cited by 43 publications

(31 citation statements)

References 90 publications

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“…1,6,41 However, this is not consistent with the emerging hypothesis that a large lipoprotein of intraocular origin may be a major molecular building block of an important pathway for constituent retinal lipid processing and the biogenesis of drusen. 42 There is circumstantial evidence that ultrastructural changes of the BM contribute to the decreased efficiency of exchange between RPE and choriocapillary vessels and facilitate the increased deposition of material in the BM with age. 43,44 Our observations are consistent with these studies.…”

Section: Discussionmentioning

confidence: 99%

Morphologic and Electroretinographic Phenotype of SR-BI Knockout Mice after a Long-Term Atherogenic Diet

Provost

Vede

Bigot

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. METHODS. Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. RESULTS. Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a-and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer.CONCLUSIONS. HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD. (Invest Ophthalmol Vis Sci. 2009; 50:3931-3942) A ge-related macular degeneration (AMD) is a complex group of diseases in which the roles of many genetic and environmental factors are intertwined. Accumulation of cholesterol under the retinal pigment epithelium (RPE) and within Bruch's membrane (BM) is a normal feature of aging, 1 but imbalances in cholesterol homeostasis may also contribute to the development of retinal diseases, including AMD. 2 Atherosclerotic cardiovascular diseases are characterized by extracellular lipid deposition in vessel walls, and retention of plasma lipoproteins in the intimae is a key event initiating atherosclerosis. 3 ApoB is a component of plasma lipoproteins and is associated with esterified cholesterol in sub-RPE lesions, such as drusen and basal deposits, in the human eye with age-related maculopathy. 4,5 These heterogeneous materials form particular abnormal structures, such as basal deposits, and have been detected by electron microscopy beneath the RPE in the BM of aged human eyes with AMD. Basal laminar deposits (BlamDs) are found between the basement membrane of the RPE and its plasma membrane and consist of basement membrane proteins and long-spacing collagen. Membranous debris including basal linear deposits (BlinDs) are localized between the RPE basement membrane and the inner collagenous zone of BM f...

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Section: Discussionmentioning

confidence: 99%

Morphologic and Electroretinographic Phenotype of SR-BI Knockout Mice after a Long-Term Atherogenic Diet

Provost

Vede

Bigot

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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“…Results of multiple studies seeking associations between measures of elevated plasma cholesterol and ARMD, or HDL levels and ARMD, have been largely inconclusive (for review, see ref. 182 ). ARMD is not considered to be associated with type 2 diabetes ( 31, 183 ), a major CAD risk factor.…”

Section: Transition From Aging (Lipid Wall) To Armd (Blind)mentioning

confidence: 99%

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

Curcio

Johnson

Huang

et al. 2010

Journal of Lipid Research

166

145

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“…Some publications suggested that statin treatment may reduce the risk of AMD [178][179][180] although others refuted this notion [181]. Given that there was no correlation between plasma apolipoprotein levels and AMD presence or severity [182], the prospects of statin use for atrophic AMD remain unclear. Alzheimer's disease plaque-forming protein amyloid-β (Aβ) is a component of drusen in atrophic AMD [183][184][185].…”

Section: Treatments Targeting Individual Components Of Drusenmentioning

confidence: 99%

New therapeutic targets in atrophic age-related macular degeneration

Petrukhin¹

2007

Expert Opinion on Therapeutic Targets

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Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. There is no effective treatment for the most prevalent atrophic (dry) form of AMD. Atrophic AMD is triggered by abnormalities in the retinal pigment epithelium (RPE) that lies beneath the photoreceptor cells and normally provides critical metabolic support to these light-sensing cells. Secondary to RPE dysfunction, macular rods and cones degenerate leading to the irreversible loss of vision. Oxidative stress, formation of drusen, accumulation of lipofuscin, local inflammation and reactive gliosis represent the pathologic processes implicated in pathogenesis of atrophic AMD. This review discusses potential target areas for small-molecule and biologic intervention, which may lead to development of new therapeutic treatments for atrophic AMD.

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Plasma apolipoproteins and risk for age related maculopathy

Cited by 43 publications

References 90 publications

Morphologic and Electroretinographic Phenotype of SR-BI Knockout Mice after a Long-Term Atherogenic Diet

Morphologic and Electroretinographic Phenotype of SR-BI Knockout Mice after a Long-Term Atherogenic Diet

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

New therapeutic targets in atrophic age-related macular degeneration

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