--- OA_place: publisher _id: '418' abstract: - lang: eng text: "The aim of this thesis was the development of new strategies for optical and optogenetic control of proliferative and pro-survival signaling, and characterizing them from the molecular mechanism up to cellular effects. These new light-based methods have unique features, such as red light as an activator, or the avoidance of gene delivery, which enable to overcome current limitations, such as light delivery to target tissues and feasibility as therapeutic approach. A special focus was placed on implementing these new light-based approaches in pancreatic β-cells, as β-cells are the key players in diabetes and especially their loss in number negatively affects disease progression. Currently no treatment options are available to compensate the lack of functional β-cells in diabetic patients.\r\nIn a first approach, red-light-activated growth factor receptors, in particular receptor tyrosine kinases were engineered and characterized. Receptor activation with light allows spatio-temporal control compared to ligand-based activation, and especially red light exhibits deeper tissue penetration than other wavelengths of the visible spectrum. Red-light-activated receptor tyrosine kinases robustly activated major growth factor related signaling pathways with a high temporal resolution. Moreover, the remote activation of the proliferative MAPK/Erk pathway by red-light-activated receptor tyrosine kinases in a pancreatic β-cell line was also achieved, through one centimeter thick mouse tissue. Although red-light-activated receptor tyrosine kinases are particularly attractive for applications in animal models due to the deep tissue penetration of red light, a drawback, especially with regard to translation into humans, is the requirement of gene therapy.\r\nIn a second approach an endogenous light-sensitive mechanism was identified and its potential to promote proliferative and pro-survival signals was explored, towards light-based tissue regeneration without the need for gene transfer. Blue-green light illumination was found to be sufficient for the activation of proliferation and survival promoting signaling pathways in primary pancreatic murine and human islets. Blue-green light also led to an increase in proliferation of primary islet cells, an effect which was shown to be mostly β-cell specific in human islets. Moreover, it was demonstrated that this approach of pancreatic β-cell expansion did not have any negative effect on the β-cell function, in particular on their insulin secretion capacity. In contrast, a trend for enhanced insulin secretion under high glucose conditions after illumination was detected. In order to unravel the detailed characteristics of this endogenous light-sensitive mechanism, the precise light requirements were determined. In addition, the expression of light sensing proteins, OPN3 and rhodopsin, was detected. The observed effects were found to be independent of handling effects such as temperature differences and cytochrome c oxidase dependent ATP increase, but they were found to be enhanced through the knockout of OPN3. The exact mechanism of how islets cells sense light and the identity of the photoreceptor remains unknown.\r\nSummarized two new light-based systems with unique features were established that enable the activation of proliferative and pro-survival signaling pathways. While red-light-activated receptor tyrosine kinases open a new avenue for optogenetics research, by allowing non-invasive control of signaling in vivo, the identified endogenous light-sensitive mechanism has the potential to be the basis of a gene therapy-free therapeutical approach for light-based β-cell expansion." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Eva full_name: Gschaider-Reichhart, Eva id: 3FEE232A-F248-11E8-B48F-1D18A9856A87 last_name: Gschaider-Reichhart orcid: 0000-0002-7218-7738 citation: ama: Gschaider-Reichhart E. Optical and optogenetic control of proliferation and survival . 2018. doi:10.15479/AT:ISTA:th_913 apa: Gschaider-Reichhart, E. (2018). Optical and optogenetic control of proliferation and survival . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_913 chicago: Gschaider-Reichhart, Eva. “Optical and Optogenetic Control of Proliferation and Survival .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_913. ieee: E. Gschaider-Reichhart, “Optical and optogenetic control of proliferation and survival ,” Institute of Science and Technology Austria, 2018. ista: Gschaider-Reichhart E. 2018. Optical and optogenetic control of proliferation and survival . Institute of Science and Technology Austria. mla: Gschaider-Reichhart, Eva. Optical and Optogenetic Control of Proliferation and Survival . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_913. short: E. Gschaider-Reichhart, Optical and Optogenetic Control of Proliferation and Survival , Institute of Science and Technology Austria, 2018. corr_author: '1' date_created: 2018-12-11T11:46:22Z date_published: 2018-01-08T00:00:00Z date_updated: 2026-04-08T14:11:54Z day: '08' ddc: - '571' - '570' degree_awarded: PhD department: - _id: HaJa doi: 10.15479/AT:ISTA:th_913 file: - access_level: closed checksum: 697fa72ca36fb1b8ceabc133d58a73e5 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-04-05T09:28:03Z date_updated: 2020-07-14T12:46:24Z file_id: '6222' file_name: 2018_THESIS_Gschaider-Reichhart_source.docx file_size: 7012495 relation: source_file - access_level: open_access checksum: 58d7d1e9e58aeb7f061ab686b1d8a48c content_type: application/pdf creator: dernst date_created: 2019-04-05T09:28:03Z date_updated: 2020-07-14T12:46:24Z file_id: '6223' file_name: 2018_THESIS_Gschaider-Reichhart.pdf file_size: 6355280 relation: main_file file_date_updated: 2020-07-14T12:46:24Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version page: '107' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7405' pubrep_id: '913' related_material: record: - id: '1678' relation: part_of_dissertation status: public - id: '1028' relation: part_of_dissertation status: public - id: '1441' relation: part_of_dissertation status: public - id: '2084' relation: part_of_dissertation status: public status: public supervisor: - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 title: 'Optical and optogenetic control of proliferation and survival ' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2018' ...