PURPOSE: To assess the effect of transforming growth factor (TGF)-β inhibitor peptides (P17 and P144) on the development of laser-induced choroidal neovascularization (LI-CNV) in a rat model. METHODS: Sixty-one Long-Evans rats underwent diode LI-CNV model. Forty-eight hours later, treatment was administered. The intravenous control group (IV-control) and intravenous P17 group (IV-17) received five doses (0.2 mg every 72 hours) of vehicle and P17, respectively. Four groups received intravitreal injections of P17 low-dose (LD-17; 1 mg/mL) and high-dose (HD-17; 20 mg/mL) and P144 low-dose (LD-144; 1 mg/mL) and high-dose (HD-144; 3 mg/mL), and fellow eyes received vehicle. CNV evolution was assessed weekly by fluorescein angiography (FA). After death, VEGF, TGF-β and PDGF protein levels were measured by ELISA in RPE and retina homogenates. Data were analyzed with commercially available statistical analysis software. RESULTS: The mean CNV area, measured in pixels, was significantly lower at the second and fourth weeks in IV-17 (P < 0.05) and from the second week in HD-17 (P < 0.05), whereas LD-144 and HD-144 showed significant differences at every time point (P < 0.05). LD-17 showed significantly lower protein levels of TGF-β in retina and PDGF in RPE (P < 0.05), whereas HD-17 showed lower levels of VEGF (RPE and retina; P < 0.05), TGF-β (RPE and retina; P < 0.05), and PDGF (RPE; P < 0.05). HD-144 showed lower VEGF levels in the retina (P < 0.05). CONCLUSIONS: TGF-β inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.
PURPOSE: To assess the effect of transforming growth factor (TGF)-β inhibitor peptides (P17 and P144) on the development of laser-induced choroidal neovascularization (LI-CNV) in a rat model. METHODS: Sixty-one Long-Evans rats underwent diode LI-CNV model. Forty-eight hours later, treatment was administered. The intravenous control group (IV-control) and intravenous P17 group (IV-17) received five doses (0.2 mg every 72 hours) of vehicle and P17, respectively. Four groups received intravitreal injections of P17 low-dose (LD-17; 1 mg/mL) and high-dose (HD-17; 20 mg/mL) and P144 low-dose (LD-144; 1 mg/mL) and high-dose (HD-144; 3 mg/mL), and fellow eyes received vehicle. CNV evolution was assessed weekly by fluorescein angiography (FA). After death, VEGF, TGF-β and PDGF protein levels were measured by ELISA in RPE and retina homogenates. Data were analyzed with commercially available statistical analysis software. RESULTS: The mean CNV area, measured in pixels, was significantly lower at the second and fourth weeks in IV-17 (P < 0.05) and from the second week in HD-17 (P < 0.05), whereas LD-144 and HD-144 showed significant differences at every time point (P < 0.05). LD-17 showed significantly lower protein levels of TGF-β in retina and PDGF in RPE (P < 0.05), whereas HD-17 showed lower levels of VEGF (RPE and retina; P < 0.05), TGF-β (RPE and retina; P < 0.05), and PDGF (RPE; P < 0.05). HD-144 showed lower VEGF levels in the retina (P < 0.05). CONCLUSIONS: TGF-β inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.
Authors: T Nakama; S Yoshida; K Ishikawa; Y Kobayashi; Y Zhou; S Nakao; Y Sassa; Y Oshima; K Takao; A Shimahara; K Yoshikawa; T Hamasaki; T Ohgi; H Hayashi; A Matsuda; A Kudo; M Nozaki; Y Ogura; M Kuroda; T Ishibashi Journal: Gene Ther Date: 2014-12-11 Impact factor: 5.250
Authors: Filip Roudnicky; Jitao David Zhang; Bo Kyoung Kim; Nikhil J Pandya; Yanjun Lan; Lisa Sach-Peltason; Heloise Ragelle; Pamela Strassburger; Sabine Gruener; Mirjana Lazendic; Sabine Uhles; Franco Revelant; Oliv Eidam; Gregor Sturm; Verena Kueppers; Klaus Christensen; Leonard D Goldstein; Manuel Tzouros; Balazs Banfai; Zora Modrusan; Martin Graf; Christoph Patsch; Mark Burcin; Claas A Meyer; Peter D Westenskow; Chad A Cowan Journal: Proc Natl Acad Sci U S A Date: 2020-08-05 Impact factor: 11.205
Authors: Bojana Jovanović; Michael W Pickup; Anna Chytil; Agnieszka E Gorska; Kimberly C Johnson; Harold L Moses; Philip Owens Journal: Cancers (Basel) Date: 2016-11-04 Impact factor: 6.639
Authors: Patricia Fernández-Robredo; Senthil Selvam; Michael B Powner; Dawn A Sim; Marcus Fruttiger Journal: PLoS One Date: 2017-01-20 Impact factor: 3.240