NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush
Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derive...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/18/10014 |
| _version_ | 1797518937530826752 |
|---|---|
| author | Pamela Rosso Elena Fico Louise A. Mesentier-Louro Viviana Triaca Alessandro Lambiase Paolo Rama Paola Tirassa |
| author_facet | Pamela Rosso Elena Fico Louise A. Mesentier-Louro Viviana Triaca Alessandro Lambiase Paolo Rama Paola Tirassa |
| author_sort | Pamela Rosso |
| collection | DOAJ |
| description | Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx). Ed-rhNGF recovers the ONC-induced alteration of GABAergic and glutamatergic markers in contralateral VCx, induces an upregulation of TrkB, which is positively correlated with BDNF precursor (proBDNF) decrease in both VCx sides, and strongly enhances TrkB+ cell soma and neuronal endings surrounded by GAD65 immuno-reactive afferents. These findings contribute to enlarging the knowledge on the mechanism of actions and cellular targets of exogenously administrated NGF, and suggest that ed-rhNGF might act by potentiating the activity-dependent TrkB expression in GAD+ cells in VCx following retina damage and/or ONC. |
| first_indexed | 2024-03-10T07:36:21Z |
| format | Article |
| id | doaj.art-fe404bfd7a614404bcfb176f76667a6f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:21Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe404bfd7a614404bcfb176f76667a6f2023-11-22T13:31:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181001410.3390/ijms221810014NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve CrushPamela Rosso0Elena Fico1Louise A. Mesentier-Louro2Viviana Triaca3Alessandro Lambiase4Paolo Rama5Paola Tirassa6National Research Council (CNR) of Italy, Institute of Biochemistry & Cell Biology (IBBC), Unit of Translational & Biomolecular Medicine “Rita Levi-Montalcini”, Viale dell’Università 33, 00185 Rome, ItalyNational Research Council (CNR) of Italy, Institute of Biochemistry & Cell Biology (IBBC), Unit of Translational & Biomolecular Medicine “Rita Levi-Montalcini”, Viale dell’Università 33, 00185 Rome, ItalyDepartment of Ophthalmology, School of Medicine, Stanford University, Stanford, CA 94305, USANational Research Council (CNR) of Italy, Institute of Biochemistry & Cell Biology (IBBC), Unit of Translational & Biomolecular Medicine “Rita Levi-Montalcini”, Viale dell’Università 33, 00185 Rome, ItalyDepartment of Sense Organs, University Sapienza of Rome, Viale del Policlinico 155, 00161 Rome, ItalySan Raffaele Hospital, Cornea and Ocular Surface Unit, Eye Repair Lab, Via Olgettina 60, 20132 Milano, ItalyNational Research Council (CNR) of Italy, Institute of Biochemistry & Cell Biology (IBBC), Unit of Translational & Biomolecular Medicine “Rita Levi-Montalcini”, Viale dell’Università 33, 00185 Rome, ItalyEye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx). Ed-rhNGF recovers the ONC-induced alteration of GABAergic and glutamatergic markers in contralateral VCx, induces an upregulation of TrkB, which is positively correlated with BDNF precursor (proBDNF) decrease in both VCx sides, and strongly enhances TrkB+ cell soma and neuronal endings surrounded by GAD65 immuno-reactive afferents. These findings contribute to enlarging the knowledge on the mechanism of actions and cellular targets of exogenously administrated NGF, and suggest that ed-rhNGF might act by potentiating the activity-dependent TrkB expression in GAD+ cells in VCx following retina damage and/or ONC.https://www.mdpi.com/1422-0067/22/18/10014BDNFneurotrophinsoptic nerve crush (ONC)synaptic transmissionrat visual cortex (VCx)GABA |
| spellingShingle | Pamela Rosso Elena Fico Louise A. Mesentier-Louro Viviana Triaca Alessandro Lambiase Paolo Rama Paola Tirassa NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush International Journal of Molecular Sciences BDNF neurotrophins optic nerve crush (ONC) synaptic transmission rat visual cortex (VCx) GABA |
| title | NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush |
| title_full | NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush |
| title_fullStr | NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush |
| title_full_unstemmed | NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush |
| title_short | NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush |
| title_sort | ngf eye administration recovers the trkb and glutamate gaba marker deficit in the adult visual cortex following optic nerve crush |
| topic | BDNF neurotrophins optic nerve crush (ONC) synaptic transmission rat visual cortex (VCx) GABA |
| url | https://www.mdpi.com/1422-0067/22/18/10014 |
| work_keys_str_mv | AT pamelarosso ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT elenafico ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT louiseamesentierlouro ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT vivianatriaca ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT alessandrolambiase ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT paolorama ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush AT paolatirassa ngfeyeadministrationrecoversthetrkbandglutamategabamarkerdeficitintheadultvisualcortexfollowingopticnervecrush |