دورية أكاديمية
أعرض في EDS

In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a potential strategy for treatment of macular degenerations.

التفاصيل البيبلوغرافية
العنوان: In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a potential strategy for treatment of macular degenerations.
المؤلفون: Kampik D; Department of Genetics, UCL Institute of Ophthalmology, London, UK.; University Hospital of Würzburg, Department of Ophthalmology, Würzburg, Germany., Basche M; Department of Genetics, UCL Institute of Ophthalmology, London, UK., Luhmann UFO; Department of Genetics, UCL Institute of Ophthalmology, London, UK.; Roche Pharmaceutical Research and Early Development, Ophthalmology Discovery & Biomarkers, Basel, Switzerland., Nishiguchi KM; Department of Genetics, UCL Institute of Ophthalmology, London, UK.; Current address: Department of Advanced Ophthalmic Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan., Williams JAE; Department of Cell Biology, UCL Institute of Ophthalmology, London, UK., Greenwood J; Department of Cell Biology, UCL Institute of Ophthalmology, London, UK., Moss SE; Department of Cell Biology, UCL Institute of Ophthalmology, London, UK., Han H; University Hospital of Würzburg, Department of Ophthalmology, Würzburg, Germany., Azam S; Department of Genetics, UCL Institute of Ophthalmology, London, UK., Duran Y; Department of Genetics, UCL Institute of Ophthalmology, London, UK., Robbie SJ; Department of Genetics, UCL Institute of Ophthalmology, London, UK., Bainbridge JWB; Department of Genetics, UCL Institute of Ophthalmology, London, UK.; Moorfields Eye Hospital, London, UK., Larkin DF; Moorfields Eye Hospital, London, UK., Smith AJ; Department of Genetics, UCL Institute of Ophthalmology, London, UK., Ali RR; Department of Genetics, UCL Institute of Ophthalmology, London, UK.; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
المصدر: Gene therapy [Gene Ther] 2017 Dec; Vol. 24 (12), pp. 810-818. Date of Electronic Publication: 2017 Nov 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5462 (Electronic) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: London : Nature Publishing Group
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Macmillan Press Ltd., c1994-
مواضيع طبية MeSH: Gene Transfer Techniques* , Genetic Therapy*, E2F2 Transcription Factor/*genetics , Macular Degeneration/*therapy , Retinal Pigment Epithelium/*physiopathology, Aging/genetics ; Aging/metabolism ; Animals ; Cell Proliferation/genetics ; Diphtheria Toxin/genetics ; Disease Models, Animal ; Genetic Vectors ; Mice ; Mice, Transgenic ; Peptide Fragments/genetics ; Regeneration ; Retinal Pigment Epithelium/cytology ; Retinal Pigment Epithelium/metabolism
مستخلص: The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration.
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معلومات مُعتمدة: NIHR-RP-011-003 United Kingdom DH_ Department of Health
المشرفين على المادة: 0 (Diphtheria Toxin)
0 (E2F2 Transcription Factor)
0 (E2f2 protein, mouse)
0 (Peptide Fragments)
0 (diphtheria toxin fragment A)
تواريخ الأحداث: Date Created: 20171201 Date Completed: 20181011 Latest Revision: 20220408
رمز التحديث: 20231215
DOI: 10.1038/gt.2017.89
PMID: 29188796
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5462
DOI:10.1038/gt.2017.89