Proceedings of the National Academy of Sciences<\/a>, the researchers describe how they compared how retinal pigmented epithelial cells\u2014which protect and maintain light-sensing photoreceptors necessary for sight\u2014changed in 3-month old and 12-month old mice after acute and chronic cigarette smoke exposure. These ages correspond to young adulthood and late middle age in humans.<\/p>\n\u201cSmoking is often assumed to accelerate aging by releasing tissue-damaging molecules called free radicals,\u201d says James T. Handa, principal investigator and chief of the retina division at the Wilmer Eye Institute at Johns Hopkins University.<\/p>\n
The new study, Handa says, shows smoking also causes epigenetic changes\u2014non-permanent shifts in gene expression that are not caused by changes in a cell\u2019s DNA sequence\u2014to retinal pigmented epithelial cells, or RPE cells, that have widespread effects on the eye and its ability to respond to environmental stress.<\/p>\n
Using genetic sequencing techniques, the team studied RPE cells from mice three, six, and 10 days after they were injected with cigarette smoke condensate, and those exposed to cigarette smoke daily for four months. The researchers were able to identify dysfunctional RPE cells and understand how chromatin accessibility\u2014the ability to physically access chromatin, a condensed structure of DNA, RNA, and proteins that control which genes are turned on or off\u2014changed post-exposure. Such changes, if found, would indicate drastic shifts in a cell\u2019s ability to adapt, function, and survive.<\/p>\n
In both young and aged mice, acute exposure to injected cigarette smoke condensate caused the formation of dysfunctional RPE clusters with decreased expression of core RPE cell function genes, decreased chromatin accessibility, and decreased expression of \u201challmarks of aging\u201d genes\u2014genes that prevent or regulate processes linked to aging. Such processes include genomic instability, shrinkage of the ends of chromosomes, and disruption of cells\u2019 energy-producing mitochondria, among others.<\/p>\n
Changes in chromatin arrangement caused by acute cigarette smoke stress limited the ability of young and aged mouse RPE cells to function, and replicated characteristics seen in humans with age-related macular degeneration, the researchers say.<\/p>\n
Notably, the researchers say, they found that a separate, distinct subset of hallmarks of aging genes were expressed only in the dysfunctional cells of young mice treated with cigarette smoke condensate, but not their aged counterparts. Similar observations were made in young and aged mice that had been exposed to cigarette smoke daily for four months.<\/p>\n
Conducting additional experiments with RPE cells donated by two people without age-related macular degeneration, or AMD, who did not smoke, one person without AMD who smoked, and one person with early AMD, the researchers identified 1,698 genes that either increased or decreased in expression and were shared between dysfunctional human and mouse RPE cells. Collectively, they suggested the shared hallmarks of aging genes may be relevant to AMD development and progression.<\/p>\n
\u201cKnowing environmental stress can interfere with the eye\u2019s ability to produce the genes needed to stay healthy, we now want to narrow down which changes are temporary and which are permanent,\u201d says Handa.<\/p>\n
Building on their findings, Handa\u2019s team plans on characterizing how age and continuous cigarette smoke exposure contributes to eye damage and comorbidities seen in patients with late-stage AMD.<\/p>\n
The study was supported by the National Institutes of Health, the Research to Prevent Blindness Stein Innovation Award, and a BrightFocus Foundation macular degeneration research grant.<\/p>\n
Handa is on the scientific advisory boards for Character Biosciences, Cirrus Pharmaceuticals, and Seeing Medicines.<\/p>\n
Source: Johns Hopkins University<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Share this Article You are free to share this article under the Attribution 4.0 International license. A new…\n","protected":false},"author":2,"featured_media":370155,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[2992,44401,39433,103,61,60],"class_list":{"0":"post-370154","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-aging","9":"tag-cigarettes","10":"tag-eyes","11":"tag-health","12":"tag-ie","13":"tag-ireland"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/370154","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=370154"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/370154\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/370155"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=370154"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=370154"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=370154"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}