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Idelalisib inhibits vitreous-induced Akt activation and proliferation of retinal pigment epithelial cells from epiretinal membranes.
Xin, Tianyi; Han, Haote; Wu, Wenyi; Huang, Xionggao; Cui, Jing; Matsubara, Joanne Aiko; Song, Jingyuan; Wang, Fang; Colyer, Marcus; Lei, Hetian.
Afiliación
  • Xin T; Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, USA; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
  • Han H; Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, USA; College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
  • Wu W; Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, USA; Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China.
  • Huang X; Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, USA; Department of Ophthalmology, Hainan Medical University, Haikou, Hainan Province, PR China.
  • Cui J; The University of British Columbia, Canada.
  • Matsubara JA; The University of British Columbia, Canada.
  • Song J; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
  • Wang F; Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • Colyer M; Department of Surgery, Walter Reed-Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Lei H; Shenzhen Eye Hospital, Shenzhen, Guangdong Province, PR China; Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, USA. Electronic address: leihetian18@hotmail.com.
Exp Eye Res ; 190: 107884, 2020 01.
Article en En | MEDLINE | ID: mdl-31786159
Proliferative vitreoretinopathy (PVR) is a blinding fibrotic eye disease that develops in 8-10% of patients who undergo primary retinal detachment-reparative surgery and in 40-60% of patients with open-globe injury. At present, there is no pharmacological treatment for this devastating disease. Vitreal growth factors activate their respective receptors of cells in the vitreous, trigger their downstream signaling transduction (e.g. phosphoinositide 3 kinases (PI3Ks)/Akt), and drive cellular responses intrinsic to the pathogenesis of PVR. PI3Ks play a central role in experimental PVR. However, which isoform(s) are involved in PVR pathogenesis remain unknown. Herein, we show that p110δ, a catalytic subunit of receptor-regulated PI3K isoform δ, is highly expressed in epiretinal membranes from patients with PVR, and that idelalisib, a specific inhibitor of PI3Kδ, effectively inhibits vitreous-induced Akt activation, proliferation, migration and contraction of retinal pigment epithelial cells derived from an epiretinal membrane of a PVR patient. Small molecules of kinase inhibitors have shown great promise as a class of therapeutics for a variety of human diseases. The data herein suggest that idelalisib is a promising PVR prophylactic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Purinas / Cuerpo Vítreo / Membrana Epirretinal / Inhibidores Enzimáticos / Proteínas Proto-Oncogénicas c-akt / Quinazolinonas / Epitelio Pigmentado de la Retina / Fosfatidilinositol 3-Quinasa Clase I Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Purinas / Cuerpo Vítreo / Membrana Epirretinal / Inhibidores Enzimáticos / Proteínas Proto-Oncogénicas c-akt / Quinazolinonas / Epitelio Pigmentado de la Retina / Fosfatidilinositol 3-Quinasa Clase I Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido