title: Expression and signaling of NGF in the healthy and injured retina.
abstract: This review summarizes the present knowledge concerning the retinal localization of the nerve growth factor (NGF), its precursor proNGF, and the receptors TrkA and p75NTRin the developing and mature rodent retina. We further discuss the changes in the expression of NGF and the receptors in experimental models of retinal disorders and diseases like inherited retinitis pigmentosa, retinal detachment, glaucoma, and diabetic retinopathy. Since proNGF is now recognized as a bioactive signaling molecule which induces cell death through p75NTRactivation, the role of proNGF in the induction of retinal cell loss under neurodegenerative conditions is also highlighted. In addition, we present the evidences for a potential therapeutic intervention with NGF for the treatment of retinal neurodegenerative diseases. Different strategies have been developed and experimentally tested in mice and rats in order to reduce cell loss and Müller cell gliosis, e.g., increasing the availability of endogenous NGF, administration of exogenous NGF, activation of TrkA, and inhibition of p75NTR. Here, we discuss the several lines of evidence supporting a protective effect of NGF on retinal cell loss, with specific emphasis on photoreceptor and retinal ganglion cell degeneration. A better understanding of the mechanisms underlying the effects of NGF and proNGF in the modulation of neurodegeneration and gliosis in the retina will help to develop efficient therapeutic strategies for various retinal diseases.
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany. Electronic address: BarataGarcia.Tarcyane@medizin.uni-leipzig.de.
authors.forename: Tarcyane Barata
authors.initials: TB
authors.lastname: Garcia
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D063928:Ependymoglial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism* / Q000628:therapy; D012164:Retinal Diseases / Q000378:metabolism* / Q000628:therapy; D015398:Signal Transduction
chemical_list: C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020932:Nerve Growth Factor
keywords: Gliosis; Neurodegeneration; Neurotrophin; Retinal disease; proNGF