Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages
Amyloid beta (Aβ) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ a...
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| description | Amyloid beta (Aβ) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse.
We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation.
Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of Aβ on outer segments may also have an impact upon visual function with age. |
| doi_str_mv | 10.1371/journal.pone.0013127 |
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We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation.
Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of Aβ on outer segments may also have an impact upon visual function with age.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0013127</identifier><identifier>PMID: 20957206</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Age ; Age related diseases ; Aging ; Aging - metabolism ; Alzheimer's disease ; Amyloid beta-Peptides - metabolism ; Animals ; Blood ; Blood vessels ; Blotting, Western ; Central nervous system ; Cognitive ability ; Deposition ; Electron microscopy ; Eye ; Eye (anatomy) ; Humans ; Immunohistochemistry ; Macrophage Activation ; Macrophages ; Macrophages - cytology ; Macular degeneration ; Macular Degeneration - metabolism ; Metabolism ; Mice ; Neuroscience ; Ophthalmology ; Ophthalmology/Macular Disorders ; Ophthalmology/Retinal Disorders ; Perfusion ; Photoreceptors ; Retina ; Retina - cytology ; Retina - metabolism ; Rodents ; Scanning electron microscopy ; Segments ; Studies ; Up-Regulation ; Visual perception ; β-Amyloid</subject><ispartof>PloS one, 2010-10, Vol.5 (10), p.e13127</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Hoh Kam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Hoh Kam et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-4017cd711935e03b98e14ef21f7166247163028ad9754c8dbe22ac18983249463</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948519/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948519/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20957206$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gendelman, Howard E.</contributor><creatorcontrib>Hoh Kam, Jaimie</creatorcontrib><creatorcontrib>Lenassi, Eva</creatorcontrib><creatorcontrib>Jeffery, Glen</creatorcontrib><title>Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Amyloid beta (Aβ) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse.
We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation.
Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of Aβ on outer segments may also have an impact upon visual function with age.</description><subject>Accumulation</subject><subject>Age</subject><subject>Age related diseases</subject><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>Blood</subject><subject>Blood vessels</subject><subject>Blotting, Western</subject><subject>Central nervous system</subject><subject>Cognitive ability</subject><subject>Deposition</subject><subject>Electron microscopy</subject><subject>Eye</subject><subject>Eye (anatomy)</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Macrophage Activation</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macular degeneration</subject><subject>Macular Degeneration - metabolism</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Neuroscience</subject><subject>Ophthalmology</subject><subject>Ophthalmology/Macular Disorders</subject><subject>Ophthalmology/Retinal Disorders</subject><subject>Perfusion</subject><subject>Photoreceptors</subject><subject>Retina</subject><subject>Retina - cytology</subject><subject>Retina - metabolism</subject><subject>Rodents</subject><subject>Scanning electron microscopy</subject><subject>Segments</subject><subject>Studies</subject><subject>Up-Regulation</subject><subject>Visual perception</subject><subject>β-Amyloid</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7jr6D0QLguLFjPlq03ghrIsfAwsLfuxtSJPTToa2GZN2da7862Z2OstUFpRAEpLnfdtzck6SPMVogSnHb9Zu8J1qFhvXwQIhTDHh95JTLCiZ5wTR-0f7k-RRCGuEMlrk-cPkhCCRcYLy0-T3lYWftqtTVcNugS2Et6mx1-ADpMH2EFJXpardNs6a9D30KlVaD-3QqN66LrVd2q_gIG_dEGUeettFrjM3d8Nm7qE-CKJbq7R3m1XUhMfJg0o1AZ6M6yz5_vHDt_PP84vLT8vzs4u55oT2c4Yw14bjGFEGiJaiAMygIrjiOM8JizNFpFBG8IzpwpRAiNK4EAUlTLCczpLne99N44IccxckJoIwKjhGkVjuCePUWm68bZXfSqesvDlwvpbK91Y3IBGtDKJCUFMxVvCy4MIYljOmSk0wLqPXu_FrQ9mC0dD1XjUT0-lNZ1eydteSCFZkMchZ8mo08O7HAKGXrQ0amkZ1EFMsC85wQSgj_yR5Fosgi8URyRd_kXenYaRqFSO1XeXiD-qdpzxjnBZZTjGL1OIOKg4DrdWxIisbzyeC1xNBZHr41ddqCEEuv375f_byasq-PGJXoJp-FVwz7EotTEG2B2PpheChun0NjOSuoQ7ZkLuGkmNDRdmz45e8FR06iP4BT98Z5g</recordid><startdate>20101001</startdate><enddate>20101001</enddate><creator>Hoh Kam, Jaimie</creator><creator>Lenassi, Eva</creator><creator>Jeffery, Glen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20101001</creationdate><title>Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages</title><author>Hoh Kam, Jaimie ; Lenassi, Eva ; Jeffery, Glen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-4017cd711935e03b98e14ef21f7166247163028ad9754c8dbe22ac18983249463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Accumulation</topic><topic>Age</topic><topic>Age related diseases</topic><topic>Aging</topic><topic>Aging - metabolism</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>Blood</topic><topic>Blood vessels</topic><topic>Blotting, Western</topic><topic>Central nervous system</topic><topic>Cognitive ability</topic><topic>Deposition</topic><topic>Electron microscopy</topic><topic>Eye</topic><topic>Eye (anatomy)</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Macrophage Activation</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macular degeneration</topic><topic>Macular Degeneration - metabolism</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Neuroscience</topic><topic>Ophthalmology</topic><topic>Ophthalmology/Macular Disorders</topic><topic>Ophthalmology/Retinal Disorders</topic><topic>Perfusion</topic><topic>Photoreceptors</topic><topic>Retina</topic><topic>Retina - cytology</topic><topic>Retina - metabolism</topic><topic>Rodents</topic><topic>Scanning electron microscopy</topic><topic>Segments</topic><topic>Studies</topic><topic>Up-Regulation</topic><topic>Visual perception</topic><topic>β-Amyloid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoh Kam, Jaimie</creatorcontrib><creatorcontrib>Lenassi, Eva</creatorcontrib><creatorcontrib>Jeffery, Glen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoh Kam, Jaimie</au><au>Lenassi, Eva</au><au>Jeffery, Glen</au><au>Gendelman, Howard E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-10-01</date><risdate>2010</risdate><volume>5</volume><issue>10</issue><spage>e13127</spage><pages>e13127-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Amyloid beta (Aβ) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse.
We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation.
Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of Aβ on outer segments may also have an impact upon visual function with age.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20957206</pmid><doi>10.1371/journal.pone.0013127</doi><tpages>e13127</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Accumulation Age Age related diseases Aging Aging - metabolism Alzheimer's disease Amyloid beta-Peptides - metabolism Animals Blood Blood vessels Blotting, Western Central nervous system Cognitive ability Deposition Electron microscopy Eye Eye (anatomy) Humans Immunohistochemistry Macrophage Activation Macrophages Macrophages - cytology Macular degeneration Macular Degeneration - metabolism Metabolism Mice Neuroscience Ophthalmology Ophthalmology/Macular Disorders Ophthalmology/Retinal Disorders Perfusion Photoreceptors Retina Retina - cytology Retina - metabolism Rodents Scanning electron microscopy Segments Studies Up-Regulation Visual perception β-Amyloid |
| title | Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages |
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