PURPOSE: To determine whether genetic ablation of the CC chemokine receptor CCR5 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neovascularization. METHODS: Wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CCR5 gene underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 and 4 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Expression of VEGF protein was quantified by ELISA. RESULTS: The mean percentages of neovascularized corneal area in control mice and CCR5-deficient mice 2 weeks after denudation were 58.3% and 38.5% (P = 0.05), respectively. At 4 weeks after denudation, the corresponding percentages were 67.6% and 44.0% (P = 0.028). In CCR5-deficient mice, VEGF protein levels were reduced 51.1% at 2 weeks (P = 0.05) after injury and 37.3% at 4 weeks (P = 0.03). CONCLUSIONS: CCR5-deficient mice showed a persistent 34% to 35% inhibition of corneal neovascularization for up to 4 weeks. This inhibition correlates with reduced expression of VEGF. These data implicate CCR5 as one essential component in the development of corneal neovascularization.
PURPOSE: To determine whether genetic ablation of the CC chemokine receptor CCR5 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neovascularization. METHODS: Wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CCR5 gene underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 and 4 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Expression of VEGF protein was quantified by ELISA. RESULTS: The mean percentages of neovascularized corneal area in control mice and CCR5-deficient mice 2 weeks after denudation were 58.3% and 38.5% (P = 0.05), respectively. At 4 weeks after denudation, the corresponding percentages were 67.6% and 44.0% (P = 0.028). In CCR5-deficient mice, VEGF protein levels were reduced 51.1% at 2 weeks (P = 0.05) after injury and 37.3% at 4 weeks (P = 0.03). CONCLUSIONS:CCR5-deficient mice showed a persistent 34% to 35% inhibition of corneal neovascularization for up to 4 weeks. This inhibition correlates with reduced expression of VEGF. These data implicate CCR5 as one essential component in the development of corneal neovascularization.
Authors: Balamurali K Ambati; Miho Nozaki; Nirbhai Singh; Atsunobu Takeda; Pooja D Jani; Tushar Suthar; Romulo J C Albuquerque; Elizabeth Richter; Eiji Sakurai; Michael T Newcomb; Mark E Kleinman; Ruth B Caldwell; Qing Lin; Yuichiro Ogura; Angela Orecchia; Don A Samuelson; Dalen W Agnew; Judy St Leger; W Richard Green; Parameshwar J Mahasreshti; David T Curiel; Donna Kwan; Helene Marsh; Sakae Ikeda; Lucy J Leiper; J Martin Collinson; Sasha Bogdanovich; Tejvir S Khurana; Masabumi Shibuya; Megan E Baldwin; Napoleone Ferrara; Hans-Peter Gerber; Sandro De Falco; Jassir Witta; Judit Z Baffi; Brian J Raisler; Jayakrishna Ambati Journal: Nature Date: 2006-10-18 Impact factor: 49.962
Authors: Surekha Maddula; Don K Davis; Soumya Maddula; Michael K Burrow; Balamurali K Ambati Journal: Ophthalmology Date: 2011-03 Impact factor: 12.079
Authors: Chandrasekharam N Nagineni; Vijay K Kommineni; Nader Ganjbaksh; Krishnasai K Nagineni; John J Hooks; Barbara Detrick Journal: Aging Dis Date: 2015-11-17 Impact factor: 6.745