title: The nerve growth factor signaling and its potential as therapeutic target for glaucoma.
abstract: Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Haitao
authors.identifier: 0000-0001-9900-8528
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Discipline of Pharmacy, School of Medical Sciences and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Bundoora, VIC 3083, Australia.
authors.forename: Thilini
authors.identifier: 0000-0003-3100-7187
authors.initials: T
authors.lastname: Thrimawithana
authors.affiliation: Discipline of Pharmacy, School of Medical Sciences and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Bundoora, VIC 3083, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
mesh_terms: D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009883:Ophthalmic Solutions / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009883:Ophthalmic Solutions; D020932:Nerve Growth Factor