دورية أكاديمية
أعرض في EDS

Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos.

التفاصيل البيبلوغرافية
العنوان: Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos.
المؤلفون: Wang X; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Wang T; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kaneko S; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kriukov E; Department of Ophthalmology, The Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA., Lam E; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Szczepan M; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Chen J; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Gregg A; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Wang X; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Fernandez-Gonzalez A; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Mitsialis SA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kourembanas S; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Baranov P; Department of Ophthalmology, The Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA., Sun Y; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. ye.sun@childrens.harvard.edu.
المصدر: Angiogenesis [Angiogenesis] 2024 Aug; Vol. 27 (3), pp. 379-395. Date of Electronic Publication: 2024 Mar 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Germany NLM ID: 9814575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7209 (Electronic) Linking ISSN: 09696970 NLM ISO Abbreviation: Angiogenesis Subsets: MEDLINE
أسماء مطبوعة: Publication: Dec. 2004- : Berlin : Springer
Original Publication: London ; Philadelphia : Rapid Science Publishers,
مواضيع طبية MeSH: Retinal Neovascularization*/metabolism , Retinal Neovascularization*/pathology , Retinal Neovascularization*/genetics , ADAM17 Protein*/metabolism , ADAM17 Protein*/genetics , Proto-Oncogene Proteins c-fos*/metabolism , Proto-Oncogene Proteins c-fos*/genetics, Animals ; Mice ; Humans ; Retinopathy of Prematurity/metabolism ; Retinopathy of Prematurity/pathology ; Retinopathy of Prematurity/genetics ; Mice, Inbred C57BL ; Transcription, Genetic ; Gene Expression Regulation ; Retinal Vessels/metabolism ; Retinal Vessels/pathology ; Retinal Rod Photoreceptor Cells/metabolism ; Retinal Rod Photoreceptor Cells/pathology ; Disease Models, Animal ; Angiogenesis
مستخلص: Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.
(© 2024. The Author(s).)
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معلومات مُعتمدة: R01HL146128 United States GF NIH HHS; R01 EY029238 United States EY NEI NIH HHS; P50 HD105351 United States HD NICHD NIH HHS; R01EY030140, R01EY029238 NIH/NEI; R01 EY030140 United States EY NEI NIH HHS; R01 HL146128 United States HL NHLBI NIH HHS; P30 EY003039 United States EY NEI NIH HHS; U24 EY029893 United States EY NEI NIH HHS
فهرسة مساهمة: Keywords: Adam17; Photoreceptor; Retinal angiogenesis; c-Fos
المشرفين على المادة: EC 3.4.24.86 (ADAM17 Protein)
0 (Proto-Oncogene Proteins c-fos)
EC 3.4.24.86 (Adam17 protein, mouse)
تواريخ الأحداث: Date Created: 20240314 Date Completed: 20240806 Latest Revision: 20240822
رمز التحديث: 20240822
مُعرف محوري في PubMed: PMC11303108
DOI: 10.1007/s10456-024-09912-0
PMID: 38483712
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7209
DOI:10.1007/s10456-024-09912-0