{"id":141254,"date":"2022-06-28T03:26:47","date_gmt":"2022-06-28T08:26:47","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2022\/06\/long-term-effects-of-human-induced-pluripotent-stem-cell-derived-retinal-cell-transplantation-in-pde6b-knockout-rats"},"modified":"2022-06-28T03:26:47","modified_gmt":"2022-06-28T08:26:47","slug":"long-term-effects-of-human-induced-pluripotent-stem-cell-derived-retinal-cell-transplantation-in-pde6b-knockout-rats","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2022\/06\/long-term-effects-of-human-induced-pluripotent-stem-cell-derived-retinal-cell-transplantation-in-pde6b-knockout-rats","title":{"rendered":"Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/long-term-effects-of-human-induced-pluripotent-stem-cell-derived-retinal-cell-transplantation-in-pde6b-knockout-rats.jpg\"><\/a><\/p>\n<p>Circa 2021 First breakthrough in immortality of the eyes of rats using the inducing of pluripotent stem cells in the eye. Which will eventually lead to immortality of the human eye.<\/p>\n<hr>\n<p>The retina is neural tissue located in the posterior part of the eye and is an extension of the central nervous system (CNS), which has limited regenerative potential once damaged<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\" title=\"London, A., Benhar, I. & Schwartz, M. The retina as a window to the brain - from eye research to CNS disorders. Nat. Rev. Neurol. 9, 44&ndash;53 (2013).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR1\" id=\"ref-link-section-d56247147e502\">1<\/a><\/sup>. Therefore, to maintain homeostasis of the retinal microenvironment and protect itself from harmful stimuli, the retina has a unique structure consisting of inner and outer blood-retinal barriers (BRBs)<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Klaassen, I., Van Noorden, C. J. F. & Schlingemann, R. O. Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog. Retin. Eye Res. 34, 19&ndash;48 (2013).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR2\" id=\"ref-link-section-d56247147e506\">2<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Kaur, C., Foulds, W. S. & Ling, E. A. Blood-retinal barrier in hypoxic ischaemic conditions: Basic concepts, clinical features and management. Prog. Retin. Eye Res. 27622&ndash;647 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR3\" id=\"ref-link-section-d56247147e506_1\">3<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Yang, J. M. et al. Dll4 suppresses transcytosis for arterial blood-retinal barrier homeostasis. Circ. Res. 126767&ndash;783 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR4\" id=\"ref-link-section-d56247147e509\">4<\/a><\/sup>. The outer BRB is mainly composed of retinal pigment epithelial (RPE) cells, which support photoreceptor cells, the primary neurons in the retina, and play a significant role in the pathogenesis of retinal degenerative disorders, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP)<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Rizzolo, L. J., Peng, S., Luo, Y. & Xiao, W. Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium. Prog. Retin. Eye Res. 30296&ndash;323 (2011).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR5\" id=\"ref-link-section-d56247147e513\">5<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Rozing, M. P. et al. Age-related macular degeneration: a two-level model hypothesis. Prog. Retin. Eye Res. 76, 100825 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR6\" id=\"ref-link-section-d56247147e513_1\">6<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Ambati, J. & Fowler, B. J. Mechanisms of age-related macular degeneration. Neuron 75, 26&ndash;39 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR7\" id=\"ref-link-section-d56247147e513_2\">7<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Chakravarthy, U. & Peto, T. Current perspective on age-related macular degeneration. JAMA. 324794&ndash;795 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR8\" id=\"ref-link-section-d56247147e513_3\">8<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795&ndash;1809 (2006).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR9\" id=\"ref-link-section-d56247147e516\">9<\/a><\/sup>. These disorders are commonly characterized by the irreversible loss of photoreceptor cells and RPE cells, and the only fundamental treatment for these retinal degenerative disorders is replacement of damaged or atrophied cells<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Gasparini, S. J., Llonch, S., Borsch, O. & Ader, M. Transplantation of photoreceptors into the degenerative retina: Current state and future perspectives. Prog. Retin. Eye Res. 69, 1&ndash;37 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR10\" id=\"ref-link-section-d56247147e520\">10<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Ikelle, L., Al-Ubaidi, M. R. & Naash, M. I. Pluripotent stem cells for the treatment of retinal degeneration: current strategies and future directions. Front. Cell Dev. Biol. 8,743 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR11\" id=\"ref-link-section-d56247147e520_1\">11<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 12\" title=\"Wang, Y., Tang, Z. & Gu, P. Stem\/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials. Cell Death Dis. 11,793 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR12\" id=\"ref-link-section-d56247147e523\">12<\/a><\/sup>. Thus, regenerative treatments, such as stem cell transplantation, are emerging as attractive options for targeting retinal degeneration that was previously considered untreatable<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 13\" title=\"Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038&ndash;1046 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR13\" id=\"ref-link-section-d56247147e527\">13<\/a><\/sup>.<\/p>\n<p>RP refers to a set of hereditary retinal degenerative disorders that initially involve photoreceptors and leads to subsequent RPE cell damage; it affects 1 in 4,000 individuals worldwide<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795&ndash;1809 (2006).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR9\" id=\"ref-link-section-d56247147e534\">9<\/a><\/sup>. Due to its inherent nature, extensive genetic studies are ongoing, and more than 50 causal genes have been identified<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 14\" title=\"Daiger, S. P., Sullivan, L. S. & Bowne, S. J. Genes and mutations causing retinitis pigmentosa. Clin. Genet. 84132&ndash;141 (2013).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR14\" id=\"ref-link-section-d56247147e538\">14<\/a><\/sup>. Among the causal genes, <i>PDE6B<\/i> is a gene that encodes rod cGMP-phosphodiesterase, which is a critical component of the biochemical light transduction pathway<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795&ndash;1809 (2006).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR9\" id=\"ref-link-section-d56247147e545\">9<\/a><\/sup>. Although various molecular and genetic studies have identified the pathomechanisms of RP, attempts to restore vision in patients with RP have failed. To overcome this issue, preclinical stem cell-based studies involving transient dosing or permanent implantation of pluripotent stem cells are being conducted<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Gasparini, S. J., Llonch, S., Borsch, O. & Ader, M. Transplantation of photoreceptors into the degenerative retina: Current state and future perspectives. Prog. Retin. Eye Res. 69, 1&ndash;37 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR10\" id=\"ref-link-section-d56247147e549\">10<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\" title=\"Ikelle, L., Al-Ubaidi, M. R. & Naash, M. I. Pluripotent stem cells for the treatment of retinal degeneration: current strategies and future directions. Front. Cell Dev. Biol. 8,743 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR11\" id=\"ref-link-section-d56247147e552\">11<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 15\" title=\"Jacobson, S. G. & Cideciyan, A. V. Treatment possibilities for retinitis pigmentosa. N. Engl. J. Med. 363, 1669&ndash;1671 (2010).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR15\" id=\"ref-link-section-d56247147e555\">15<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 16\" title=\"Singh, M. S. et al. Retinal stem cell transplantation: balancing safety and potential. Prog. Retin. Eye Res. 75, 100779 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s12276-021-00588-w#ref-CR16\" id=\"ref-link-section-d56247147e558\">16<\/a><\/sup>.<\/p>\n<p>Permanent implantation of retinal stem cells is a promising method and is highly expected to be a potential alternative treatment strategy for replacing damaged retinal cells<sup>13,16<\/sup>. Sharma <i>et al.<\/i><sup>17<\/sup> manufactured clinical-grade AMD patient stem cell-derived RPE cells using RPE patches of a biodegradable scaffold, and functionally validated the effects of their transplantation. This researchers provided a pipeline for the generation of clinical-grade induced pluripotent stem cell (iPSC)-derived RPE cells, and histologically and functionally validated the efficacy of transplantation, thereby significantly advancing the retinal stem cell transplantation field; however, a single RPE cell transplantation cannot rescue already compromised photoreceptor cells and can be only applied in early stages of retinal degenerative diseases, when there are sufficient functional photoreceptor cells.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Circa 2021 First breakthrough in immortality of the eyes of rats using the inducing of pluripotent stem cells in the eye. Which will eventually lead to immortality of the human eye. The retina is neural tissue located in the posterior part of the eye and is an extension of the central nervous system (CNS), which [\u2026]<\/p>\n","protected":false},"author":513,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,19,412,269,47],"tags":[],"class_list":["post-141254","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-chemistry","category-genetics","category-life-extension","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/141254","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/513"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=141254"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/141254\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=141254"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=141254"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=141254"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}