Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2...Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.展开更多
Both inflammation and anti-inflammation are involved in the protection of retinal cells.Antagonists of the hypothalamic growth hormone-releasing hormone receptor(GHRHR)have been shown to possess potent anti-inflammato...Both inflammation and anti-inflammation are involved in the protection of retinal cells.Antagonists of the hypothalamic growth hormone-releasing hormone receptor(GHRHR)have been shown to possess potent anti-inflammatory properties in experimental disease models of various organs,some with systemic complications.Such effects are also found in ocular inflammatory and neurologic injury studies.In experimental models of mice and rats,both growth hormone-releasing hormone receptor agonists and antagonists may alleviate death of ocular neural cells under certain experimental conditions.This review explores the properties of growth hormone-releasing hormone receptor agonists and antagonists that lead to its protection against inflammatory responses induced by extrinsic agents or neurologic injures in ocular animal models.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81570849,81100931the Natural Science Foundation of Guangdong Province of China,Nos.2015A030313446,2020A1515011413(all to LPC).
文摘Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.
基金supported by the National Natural Science Foundation of China(81570849 to LPC)Joint Regional Basic Science and Applied Basic Science Research Fund of Guangdong Province(2019 A1515110685 to TKN)+4 种基金Special Fund for Chinese Medicine Development of Guangdong Province(20202089 to TKN)the Natural Science Foundation of Guangdong Province(2020 A1515010415 to LPC)an internal grant from Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong KongGrant for Key Disciplinary Project of Clinical Medicine under the Guangdong High-level University Development Program, ChinaThe Chinese University of Hong Kong Direct Grant(2020.067 to WKC)
文摘Both inflammation and anti-inflammation are involved in the protection of retinal cells.Antagonists of the hypothalamic growth hormone-releasing hormone receptor(GHRHR)have been shown to possess potent anti-inflammatory properties in experimental disease models of various organs,some with systemic complications.Such effects are also found in ocular inflammatory and neurologic injury studies.In experimental models of mice and rats,both growth hormone-releasing hormone receptor agonists and antagonists may alleviate death of ocular neural cells under certain experimental conditions.This review explores the properties of growth hormone-releasing hormone receptor agonists and antagonists that lead to its protection against inflammatory responses induced by extrinsic agents or neurologic injures in ocular animal models.
