Lipids of bovine retinal pigment epithelium

Anderson, Robert E.; Lissandrello, Patricia M.; Maude, Maureen B.; Matthes, Michael T.

doi:10.1016/0014-4835(76)90198-6

Cited by 35 publications

(16 citation statements)

References 10 publications

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“…Because DHA is concentrated in RPE and photoreceptor cells [14][15][16] , we reasoned that these tissues are a probable source of CEP adducts during aging. Because serum albumin is one of the major proteins modified with CEP in people with AMD 2 , we immunized mice with CEPmodified mouse serum albumin (CEP-MSA) in an attempt to raise the level of sensitivity to endogenously generated CEP (Fig.…”

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confidence: 99%

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Oxidative damage–induced inflammation initiates age-related macular degeneration

Hollyfield

Bonilha

Rayborn

et al. 2008

Nat Med

631

532

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Oxidative damage and inflammation are postulated to be involved in age-related macular degeneration (AMD). However, the molecular signal(s) linking oxidation to inflammation in this late-onset disease is unknown. Here we describe AMD-like lesions in mice after immunization with mouse serum albumin adducted with carboxyethylpyrrole, a unique oxidation fragment of docosahexaenoic acid that has previously been found adducting proteins in drusen from AMD donor eye tissues 1 and in plasma samples 2 from individuals with AMD. Immunized mice develop antibodies to this hapten, fix complement component-3 in Bruch's membrane, accumulate drusen below the retinal pigment epithelium during aging, and develop lesions in the retinal pigment epithelium mimicking geographic atrophy, the blinding end-stage condition characteristic of the dry form of AMD. We hypothesize that these mice are sensitized to the generation of carboxyethylpyrrole adducts in the outer retina, where docosahexaenoic acid is abundant and conditions for oxidative damage are permissive. This new model provides a platform for dissecting the molecular pathology of oxidative damage in the outer retina and the immune response contributing to AMD.AMD is the most common cause of legal blindness in elderly individuals of industrialized countries 3,4 . Clinicians have long recognized that debris (termed drusen) below the retinal pigment epithetlium (RPE) in the macula is a risk factor for AMD. The presence of complement factor proteins in drusen in AMD eyes 1,5-7 and genetic variation in several complement factor genes in individuals with AMD 8-13 implicate inflammation as an important component in this disease. However, little is known about the signal(s) from the outer retina that initiates the immune system's involvement in AMD.As a potential initiating signal we evaluated carboxyethylpyrrole (CEP; Fig. 1a), an adduct that forms from an oxidation fragment of docosahexaenoic acid (DHA) 2 . DHA, the most oxidizable

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confidence: 99%

“…of all long-chain polyunsaturated fatty acids, is abundant in the outer retina, where high oxygen tension and light provide a permissive environment for oxidation [14][15][16] . CEP forms when the aldehyde group on a newly formed seven-carbon oxidation fragment of DHA covalently interacts with an ε-lysyl amino group in a tissue protein 1,2 .…”

mentioning

confidence: 99%

Oxidative damage–induced inflammation initiates age-related macular degeneration

Hollyfield

Bonilha

Rayborn

et al. 2008

Nat Med

631

532

View full text Add to dashboard Cite

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“…DHA had little effect on the interactions of retinal in the retinoid-binding site 1, nor did it alter the interactions of retinol in either of its IRBP binding sites. The ability of this fatty acid to speci®cally facilitate the dissociation of 11-cis-retinal from IRBP, and the observations that photoreceptor cells are greatly enriched in DHA (Anderson et al, 1976;Chen et al, 1996) suggest that DHA it may function as thè switch' that allows the protein to target 11-cis-retinal to photoreceptor cells (Chen et al, 1996). The ligandand site-speci®city of the DHA-elicited response of IRBP implies that the`second retinoid-binding site' of IRBP is composed of two distinct sites, one which is selective for 11-cis-retinal and is regulated by DHA, and another which is speci®c for all-trans-retinol and is not affected by the fatty acid.…”

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confidence: 96%

Interphotoreceptor Retinoid-binding Protein Contains Three Retinoid Binding Sites

Shaw

Noy

2001

Experimental Eye Research

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“…DHA is the most oxidizable of all long chain fatty acids with 22 carbons and six double bonds (22:6w3). DHA is highly concentrated in photoreceptors and the RPE, accounting for approximately 40% of the fatty acids in photoreceptor outer segment membranes (43,44). These DHA-rich membranes reside in a compartment rich in oxygen and light, conditions that are highly permissive for oxidative damage (43)(44)(45).…”

mentioning

confidence: 99%

“…DHA is highly concentrated in photoreceptors and the RPE, accounting for approximately 40% of the fatty acids in photoreceptor outer segment membranes (43,44). These DHA-rich membranes reside in a compartment rich in oxygen and light, conditions that are highly permissive for oxidative damage (43)(44)(45). Proteins isolated from drusen and Bruch's membrane are adducted with carboxyethylpyrrole (CEP), a novel adduct that can only be produced by the oxidative fragmentation of DHA (21).…”

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confidence: 99%

Animal Models for Age-Related Macular Degeneration

Hollyfield

Kuttner-Kondo

2009

Neuromethods

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Age-related macular degeneration (AMD) has a number of characteristic features including late onset and accumulation of deposits (drusen) below the retinal pigment epithelium on Bruch's membrane in the macula. A progressive increase in these deposits (in some individuals) leads to macular blindness, following either the local loss of the retinal pigment epithelium (geographic atrophy) or the hemorrhage of new blood vessels that originate in the choroid and invade the compartment between the photoreceptors and retinal pigment epithelium (choroidal neovascularization). Over the last few years a number of mouse models for AMD have been described that replicate some of the changes manifest in the human disease. This chapter begins with a description of the hallmarks of AMD, discusses some of the ideas about the underlying mechanisms and then summarizes the features of AMD found in experimental animals that are purported to model this disorder.Key words: Age-related macular degeneration (AMD), Drusen, Bruch's membrane, Geographic atrophy, Choroidal neovascularization, AMD animal model Age-related macular degeneration (AMD) constitutes a major cause of legal blindness in the elderly population of developed countries. Millions of individuals over 55 years of age are blind from AMD in Europe and North America with over 300,000 new AMD cases presenting annually (1, 2). In some individuals, in addition to the normal age-related thickening of Bruch's membrane, focal accumulation of debris on Bruch's membrane causes nodular elevations of the RPE that are recognized in an eye exam as drusen (3-5). Clinicians have long recognized that the presence of drusen in the macula, their size, density, and the area encompassed by these deposits represent early stages in the AMD disease process. While the initial drusen deposits are not associated with 1. Age-related macular degeneration: The Human Condition

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Lipids of bovine retinal pigment epithelium

Cited by 35 publications

References 10 publications

Oxidative damage–induced inflammation initiates age-related macular degeneration

Oxidative damage–induced inflammation initiates age-related macular degeneration

Interphotoreceptor Retinoid-binding Protein Contains Three Retinoid Binding Sites

Animal Models for Age-Related Macular Degeneration

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