title: Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat.
abstract: BACKGROUND
  The neurotrophin nerve growth factor (NGF) is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO) is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days) after bilateral carotid occlusion.
  
  
  RESULTS
  We demonstrated that a single intravitreal injection of NGF (5 microg/3 microl performed 24 hours after 2VO ligation) has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and c-jun- expression (at 8 days after 2VO). A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO), as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression.
  
  
  CONCLUSIONS
  The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.
authors.affiliation: DIMORFIPA, University of Bologna, Bologna, Italy. sandra.sivilia@unibo.it
authors.forename: Sandra
authors.initials: S
authors.lastname: Sivilia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Turba
authors.forename: Monica
authors.initials: M
authors.lastname: Forni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Massella
authors.forename: Nadia
authors.initials: N
authors.lastname: De Sordi
authors.forename: Luciana
authors.initials: L
authors.lastname: Giardino
authors.forename: Laura
authors.initials: L
authors.lastname: Calzà
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002340:Carotid Artery Diseases / Q000150:complications*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009901:Optic Nerve Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012025:Reflex, Pupillary / Q000187:drug effects; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004676:Myelin Basic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D014404:Tubulin; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor; D020917:Receptor, trkA