{"id":35517,"date":"2021-09-06T06:11:16","date_gmt":"2021-09-06T06:11:16","guid":{"rendered":"https:\/\/www.elza-institute.com\/?p=35517"},"modified":"2021-10-01T11:39:04","modified_gmt":"2021-10-01T11:39:04","slug":"new-insights-into-ehlers-danlos-syndrome","status":"publish","type":"post","link":"https:\/\/www.elza-institute.com\/pt\/new-insights-into-ehlers-danlos-syndrome\/","title":{"rendered":"Novos conhecimentos sobre a s\u00edndrome de Ehlers-Danlos"},"content":{"rendered":"<p><strong><em>Investigadores do ELZA, da ETH Zurich, da Universidade de Zurique e da Universidade do Sul da Florida investigam a biomec\u00e2nica da c\u00f3rnea num modelo de rato para Ehlers-Danlos<\/em><\/strong><\/p>\n<p>Ter uma c\u00f3rnea fraca pode ser mau para a vis\u00e3o - e pode, em \u00faltima an\u00e1lise, levar \u00e0 cegueira, raz\u00e3o pela qual existem esfor\u00e7os intensos de investiga\u00e7\u00e3o para compreender porque \u00e9 que algumas c\u00f3rneas ficam fracas e outras n\u00e3o. Mas h\u00e1 um problema. Na maioria das outras doen\u00e7as, os modelos de ratinhos transg\u00e9nicos podem ser utilizados para compreender melhor as doen\u00e7as, mas avaliar a for\u00e7a da c\u00f3rnea - ou \"biomec\u00e2nica\" - em olhos de ratinhos \u00e9 um grande desafio. Os m\u00e9todos que medem a for\u00e7a da c\u00f3rnea, como a extensometria, que consiste em cortar uma tira da c\u00f3rnea e estic\u00e1-la numa dimens\u00e3o, e avaliar a velocidade a que se estica e a for\u00e7a necess\u00e1ria para quebrar a tira, s\u00e3o muito mais dif\u00edceis de executar com precis\u00e3o e de forma reprodut\u00edvel em olhos de ratinho do que em olhos de animais maiores, como os porcos.<\/p>\n<p>Mas os investigadores da ETH Zurich (<a href=\"https:\/\/www.ethz.ch\/\">www.ethz.ch<\/a>), a Universidade de Zurique (<a href=\"https:\/\/www.cabmm.uzh.ch\/\">www.cabmm.uzh.ch<\/a>), da Universidade do Sul da Florida, e cl\u00ednicos do Instituto ELZA, Zurique (<a href=\"https:\/\/www.elza-institute.com\/pt\/\">www.elza-institute.com<\/a>), adaptaram previamente esta abordagem \u00e0s dimens\u00f5es extra-pequenas dos olhos<sup>1<\/sup>e acrescentou agora uma t\u00e9cnica inovadora, a elastografia de coer\u00eancia \u00f3tica (OCE), e um m\u00e9todo de imagem avan\u00e7ado, a microscopia de segunda gera\u00e7\u00e3o harm\u00f3nica (SHG), a fim de comparar ratinhos com uma defici\u00eancia gen\u00e9tica de colag\u00e9nio V <sup>2<\/sup>um modelo para a s\u00edndrome de Ehlers-Danlos. O colag\u00e9nio V \u00e9 um componente importante da parte estrutural da c\u00f3rnea, chamada estroma, mas os ratinhos transg\u00e9nicos em que ambas as c\u00f3pias do\u00a0<em>Col5a1<\/em>\u00a0n\u00e3o se desenvolvem para al\u00e9m do dia embrion\u00e1rio 10-11. No entanto, os ratinhos heterozig\u00f3ticos (<em>Col5a1+\/-<\/em>) sobrevivem, sendo que as c\u00f3rneas destes ratinhos t\u00eam menos fibrilhas de colag\u00e9nio do que as dos seus companheiros de ninhada de tipo selvagem (WT).<\/p>\n<p>Com as t\u00e9cnicas experimentais aplicadas, os investigadores puderam avaliar a tens\u00e3o na c\u00f3rnea - por outras palavras, a quantidade e a rapidez com que a c\u00f3rnea muda de forma e tamanho em resposta a uma for\u00e7a que lhe \u00e9 aplicada. As experi\u00eancias de extensometria de pequena dimens\u00e3o mostraram diferen\u00e7as entre os dois grupos. Em compara\u00e7\u00e3o com as c\u00f3rneas WT, as c\u00f3rneas heterozigotas tinham uma probabilidade 25-30% maior de se romperem durante as experi\u00eancias de extensometria - algo que se observa na cl\u00ednica, onde cerca de 35% dos doentes com s\u00edndrome de Ehlers-Danlos sofrem rupturas da c\u00f3rnea, quer espontaneamente <sup>3<\/sup> ou em resposta a um traumatismo m\u00ednimo, uma condi\u00e7\u00e3o denominada \"oculus fragilis\" <sup>\u00a0<\/sup><sup>4<\/sup>. Al\u00e9m disso, as c\u00f3rneas tornaram-se significativamente mais relaxadas ap\u00f3s a aplica\u00e7\u00e3o de uma carga. Para a elastografia, todo o conjunto experimental estava contido numa c\u00e2mara de press\u00e3o selada, e a for\u00e7a aplicada era uma altera\u00e7\u00e3o na press\u00e3o da c\u00e2mara. As experi\u00eancias de OCE mostraram que as c\u00f3rneas heterozigotas eram significativamente mais finas do que as c\u00f3rneas WT, mas capazes de suportar a mesma quantidade de tens\u00e3o axial que as c\u00f3rneas do tipo selvagem. Ap\u00f3s o ajuste para a espessura da c\u00f3rnea, isso significava que as c\u00f3rneas heterozigotas tinham uma rigidez mec\u00e2nica maior do que as c\u00f3rneas do tipo selvagem. As imagens SHG indicaram que as c\u00f3rneas heterozig\u00f3ticas apresentavam \"desorganiza\u00e7\u00e3o das fibrilas, aumento da densidade das fibrilas e anomalias na organiza\u00e7\u00e3o hier\u00e1rquica\", em compara\u00e7\u00e3o com as c\u00f3rneas de tipo selvagem.<\/p>\n<p>A primeira autora do estudo, a Dra. Sabine Kling, da ETH Zurich, explicou o significado do seu trabalho: \"Demonstr\u00e1mos que os tecidos podem apresentar um comportamento de deforma\u00e7\u00e3o distinto, dependendo do tipo e da velocidade a que a carga \u00e9 aplicada. Por conseguinte, um \u00fanico teste de carateriza\u00e7\u00e3o n\u00e3o poderia ter fornecido estas informa\u00e7\u00f5es sobre o impacto mec\u00e2nico de\u00a0<em>col5<\/em>\u00a0no tecido da c\u00f3rnea como obtivemos aqui\".<\/p>\n<p>Farhad Hafezi, MD PhD afirma que \"as nossas descobertas fornecem mais informa\u00e7\u00f5es e podem ajudar a desenvolver abordagens terap\u00eauticas em c\u00f3rneas fr\u00e1geis\".<\/p>\n<p>O texto completo do artigo est\u00e1 dispon\u00edvel para leitura aqui:\u00a0<a href=\"https:\/\/rdcu.be\/cwlU1\">https:\/\/rdcu.be\/cwlU1<\/a><\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Refer\u00eancias<\/strong><\/p>\n<ol>\n<li>Hammer A, Kling S, Boldi M-O, et al. Estabelecimento de liga\u00e7\u00f5es cruzadas da c\u00f3rnea com riboflavina e uv-a na c\u00f3rnea do rato in vivo: an\u00e1lise biomec\u00e2nica.\u00a0<em>Invest Ophthalmol Vis Sci<\/em>. 56(11):6581-6590 (2015).<\/li>\n<li>Kling S, Torres-Netto EA, Abdshahzadeh H, Espana EM, Hafezi F. A insufici\u00eancia de colag\u00e9nio V num modelo de rato para a s\u00edndrome de Ehlers Danlos afecta as propriedades biomec\u00e2nicas viscoel\u00e1sticas, explicando as c\u00f3rneas finas e fr\u00e1geis. Sci Rep 11(1):17362. (2021).<\/li>\n<li>Cameron, J. A. Corneal abnormalities in Ehlers-Danlos syndrome type VI (Anomalias da c\u00f3rnea na s\u00edndrome de Ehlers-Danlos tipo VI). Cornea 12, 54-59 (1993).<\/li>\n<\/ol>","protected":false},"excerpt":{"rendered":"<p>Researchers from ELZA, the ETH Zurich, the University of Zurich and the University of South Florida investigate corneal biomechanics in a mouse model for Ehlers-Danlos syndrome Having a weak cornea can be bad for your sight &#8211; and can ultimately lead to blindness, which is why there are intense research efforts into understanding why some [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":35518,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[243,214,215,95],"tags":[132,125,275,495,497,496],"class_list":["post-35517","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-emilio-torres","category-farhad-hafezi","category-sabine-kling","category-scientific-article","tag-biomechanics","tag-cornea","tag-corneal-biomechanics","tag-ehlers-danlos","tag-strength","tag-transgenic-mice"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - 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