Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 3/2015

01-09-2015 | Original Paper

NGF Expression in Reelin-Deprived Retinal Cells: A Potential Neuroprotective Effect

Authors: Bijorn Omar Balzamino, Graziana Esposito, Ramona Marino, Flavio Keller, Alessandra Micera

Published in: NeuroMolecular Medicine | Issue 3/2015

Login to get access

Abstract

We recently reported that increased NGF and p75NTR as well as decreased trkANGFR characterized the Reelin-deprived (E-Reeler) retina, prospecting a potential contribution of NGF during E-Reeler retinogenesis. Herein, retinal ganglion cells (RGCs), glial cells and rod bipolar cells (RBCs) were isolated from E-Reeler retinas, and NGF, trkANGFR/p75NTR expression and apoptosis were investigated. E-Reeler (n = 28) and E-control (n = 34) retinas were digested, and RGCs, glial cells and RBCs were isolated by the magnetic bead separation. Expression of NGF, trkANGFR, p75NTR, Annexin V/PI and Bcl2/Bax was quantified by flow cytometry and validated by real-time PCR or WB. In E-Reeler retinas, NGF was significantly increased in RGCs and glial cells, p75NTR was increased in both RBCs and RGCs, and trkANGFR was unchanged. In E-control retinas, NGF and p75NTR were expressed mainly in RBCs and RGCs and faintly in glial cells, while trkANGFR was weakly expressed by RBCs and RGCs. In RBCs and RGCs, Annexin V expression was unchanged, while Bcl2 increased and Bax decreased selectively in E-Reeler RGCs. The data indicate that E-Reeler RBCs and RGCs overexpress NGF and p75NTR as a protective endogenous response to Reelin deprivation. The observation is strongly supported by the absence of apoptosis in both cell types.
Literature
Aloe, L., Tirassa, P., & Lambiase, A. (2008). The topical application of nerve growth factor as a pharmacological tool for human corneal and skin ulcers. Pharmacological Research, 57(4), 253–258.CrossRefPubMed
Angelucci, C., Maulucci, G., Lama, G., Proietti, G., Colabianchi, A., Papi, M., et al. (2012). Epithelial-stromal interactions in human breast cancer: Effects on adhesion, plasma membrane fluidity and migration speed and directness. PLoS One, 7(12), e50804.PubMedCentralCrossRefPubMed
Bai, Y., Dergham, P., Nedev, H., Xu, J., Galan, A., Rivera, J. C., et al. (2012). Chronic and acute models of retinal neurodegeneration TrkA activity are neuroprotective whereas p75NTR activity is neurotoxic through a paracrine mechanism. Journal of Biological Chemistry, 285(50), 39392–39400.CrossRef
Balzamino, B. O., Biamonte, F., Esposito, G., Marino, R., Fanelli, F., Keller, F., & Micera, A. (2014). Characterization of NGF, trkANGFR and p75NTR in retina of mice lacking Reelin glycoprotein. International Journal of Cell Biology, 2014, 725928.PubMedCentralCrossRefPubMed
Bandtlow, C., & Dechant, G. (2004). From cell death to neuronal regeneration, effects of the p75 neurotrophin receptor depend on interactions with partner subunits. Science STKE, 2004, pe24.
Barnstable, C. J., & Drager, U. C. (1984). Thy-1 antigen: A ganglion cell specific marker in rodent retina. Neuroscience, 11(4), 847–855.CrossRefPubMed
Berardi, N., Cellerino, A., Domenici, L., Fagiolini, M., Pizzorusso, T., Cattaneo, A., & Maffei, L. (1994). Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system. Proceedings of the National Academy of Sciences USA, 91(2), 684–688.CrossRef
Berardi, N., Lodovichi, C., Caleo, M., Pizzorusso, T., & Maffei, L. (1999). Role of neurotrophins in neural plasticity: What we learn from the visual cortex. Restorative Neurology and Neuroscience, 15(2–3), 125–136.PubMed
Berardi, N., & Maffei, L. (1999). From visual experience to visual function: Roles of neurotrophins. Journal of Neurobiology, 41(1), 119–126.CrossRefPubMed
Bonfanti, L., Strettoi, E., Chierzi, S., Cenni, M. C., Liu, X. H., Martinou, J. C., et al. (1996). Protection of retinal ganglion cells from natural and axotomy-induced cell death in neonatal transgenic mice overexpressing bcl-2. Journal of Neuroscience, 16(13), 4186–4194.PubMed
Carmignoto, G., Comelli, M. C., Candeo, P., Cavicchioli, L., Yan, Q., Merighi, A., & Maffei, L. (1991). Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina. Experimental Neurology, 111(3), 302–311.CrossRefPubMed
Carmignoto, G., Maffei, L., Candeo, P., Canella, R., & Comelli, C. (1989). Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. Journal of Neuroscience, 9(4), 1263–1272.PubMed
Chao, M. V., & Hempstead, B. L. (1995). p75 and Trk: A two-receptor system. Trends in Neuroscience, 18(7), 321–326.CrossRef
Chen, D. F., Jhaveri, S., & Schneider, G. E. (1995). Intrinsic changes in developing retinal neurons result in regenerative failure of their axons. Proceedings of the National Academy of Sciences USA, 92(16), 7287–7291.CrossRef
Coassin, M., Lambiase, A., Sposato, V., Micera, A., Bonini, S., & Aloe, L. (2008). Retinal p75 and Bax overexpression is associated with retinal ganglion cells apoptosis in a rat model of glaucoma. Graefe’s Archive for Clinical and Experimental Ophthalmology, 246(12), 1743–1749.CrossRefPubMed
Colafrancesco, V., Coassin, M., Rossi, S., & Aloe, L. (2011). Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration. Annuali dell’Istituto Superiore di Sanità, 47(3), 284–289.
Cui, Q., Tang, L. S., Hu, B., So, K. F., & Yip, H. K. (2002). Expression of trkA, trkB, and trkC in injured and regenerating retinal ganglion cells of adult rats. Investigative Ophthalmology & Visual Science, 43(6), 1954–1964.
D’Arcangelo, G., Miao, G. G., Chen, S. C., Soares, H. D., Morgan, J. I., & Curran, T. (1995). A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature, 374(6524), 719–723.CrossRefPubMed
D’Arcangelo, G., Miao, G. G., & Curran, T. (1996). Detection of the reelin breakpoint in reeler mice. Molecular Brain Research, 39(1–2), 234–236.CrossRefPubMed
Förster, E., Bock, H. H., Herz, J., Chai, X., Frotscher, M., & Zhao, S. (2010). Emerging topics in Reelin function. European Journal of Neuroscience, 31(9), 1511–1518.PubMedCentralPubMed
Gragnani, A., Ipolito, M. Z., Sobral, C. S., Brunialti, M. K., Salomão, R., & Ferreira, L. M. (2008). Flow cytometry of human primary epidermal and follicular keratinocytes. Eplasty, 8, e14.PubMedCentralPubMed
Guo, X. J., Tian, X. S., Ruan, Z., Chen, Y. T., Wu, L., Gong, Q., et al. (2014). Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina. Experimental Eye Research, 125, 156–163.CrossRefPubMed
Ha, Y., Shanmugam, A. K., Markand, S., Zorrilla, E., Ganapathy, V., & Smith, S. B. (2014). Sigma receptor 1 modulates ER stress and Bcl2 in murine retina. Cell Tissue Research, 356(1), 15–27.PubMedCentralCrossRefPubMed
Harada, C., Harada, T., Nakamura, K., Sakai, Y., Tanaka, K., & Parada, L. F. (2006). Effect of p75NTR on the regulation of naturally occurring cell death and retinal ganglion cell number in the mouse eye. Developmental Biology, 290(1), 57–65.CrossRefPubMed
Jeon, C. J., Strettoi, E., & Masland, R. H. (1998). The major cell populations of the mouse retina. Journal of Neuroscience, 18(21), 8936–8946.PubMed
Khialeeva, E., Lane, T. F., & Carpenter, E. M. (2011). Disruption of reelin signaling alters mammary gland morphogenesis. Development, 138(4), 767–776.PubMedCentralCrossRefPubMed
Kim, Y. S., Jo, D. H., Lee, H., Kim, J. H., Kim, K. W., & Kim, J. H. (2013). Nerve growth factor-mediated vascular endothelial growth factor expression of astrocyte in retinal vascular development. Biochemical and Biophysical Research Communications, 431(4), 740–745.CrossRefPubMed
Lambiase, A., Coassin, M., Tirassa, P., Mantelli, F., & Aloe, L. (2009). Nerve growth factor eye drops improve visual acuity and electrofunctional activity in age-related macular degeneration: A case report. Annuali Istituto Superiore di Sanità, 45(4), 439–442.
Lameirão, S. V., Hamassaki, D. E., Rodrigues, A. R., DE Lima, S. M., Finlay, B. L., & Silveira, L. C. (2009). Rod bipolar cells in the retina of the capuchin monkey (Cebus apella): Characterization and distribution. Visual Neuroscience, 26(4), 389–396.CrossRefPubMed
Lebrun-Julien, F., Morquette, B., Douillette, A., Saragovi, H. U., & Di Polo, A. (2009). Inhibition of p75(NTR) in glia potentiates TrkA-mediated survival of injured retinal ganglion cells. Molecular Cell Neuroscience, 40(4), 410–420.CrossRef
Levi-Montalcini, R. (1987). The nerve growth factor 35 years later. Science, 237(4819), 1154–1162.CrossRefPubMed
Lin, S. F., Mao, Y. X., Li, B., Sun, W., & Tang, S. B. (2013). Morphological and immunocytochemical analysis of human retinal glia subtypes in vitro. International Journal of Ophthalmolology, 6(5), 559–563.
Maffei, L., Berardi, N., Domenici, L., Parisi, V., & Pizzorusso, T. (1992). Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats. Journal of Neuroscience, 12(12), 4651–4662.PubMed
Masu, M., Iwakabe, H., Tagawa, Y., Miyoshi, T., Yamashita, M., Fukuda, Y., et al. (1995). Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell, 80(5), 757–765.CrossRefPubMed
Micera, A., Lambiase, A., Puxeddu, I., Aloe, L., Stampachiacchiere, B., Levi-Schaffer, F., et al. (2006). Nerve growth factor effect on human primary fibroblastic-keratocytes: Possible mechanism during corneal healing. Experimental Eye Research, 83(4), 747–757.CrossRefPubMed
Micera, A., Lambiase, A., Stampachiacchiere, B., Bonini, S., Bonini, S., & Levi-Schaffer, F. (2007). Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate. Cytokine and Growth Factor Review, 18(3–4), 245–256.CrossRef
Micera, A., Puxeddu, I., Balzamino, B. O., Bonini, S., & Levi-Schaffer, F. (2012). Chronic nerve growth factor exposure increases apoptosis in a model of in vitro induced conjunctival myofibroblasts. PLoS One, 7(10), e47316.PubMedCentralCrossRefPubMed
Nadal-Nicolás, F. M., Jiménez-López, M., Sobrado-Calvo, P., Nieto-López, L., Cánovas-Martínez, I., Salinas-Navarro, M., et al. (2009). Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naive and optic nerve-injured retinas. Investigative Ophthalmology & Visual Science, 50(8), 3860–3868.CrossRef
Nakamura, K., Harada, C., Okumura, A., Namekata, K., Mitamura, Y., Yoshida, K., et al. (2005). Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse. Molecular Vision, 11, 1229–1235.PubMed
Nirenberg, S., & Meister, M. (1997). The light response of retinal ganglion cells is truncated by a displaced amacrine circuit. Neuron, 18(4), 637–650.CrossRefPubMed
Oberdick, J., Smeyne, R. J., Mann, J. R., Zackson, S., & Morgan, J. I. (1990). A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science, 248(4952), 223–226.CrossRefPubMed
Portillo, J. A., Okenka, G., Kern, T. S., & Subauste, C. S. (2009). Identification of primary retinal cells and ex vivo detection of proinflammatory molecules using flow cytometry. Molecular Vision, 15, 1383–1389.PubMedCentralPubMed
Pulido, J. S., Sugaya, I., Comstock, J., & Sugaya, K. (2007). Reelin expression is upregulated ocular tissue injury. Graefe’s Archive for Clinical and Experimental Ophthalmology, 245(6), 889–893.CrossRefPubMed
Rice, D. S., Nusinowitz, S., Azimi, A. M., Martínez, A., Soriano, E., & Curran, T. (2001). The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron, 31(6), 929–941.CrossRefPubMed
Rodriguez-Tébar, A., Dechant, G., & Barde, Y. A. (1990). Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron, 4(4), 487–492.CrossRefPubMed
Samuel, M. A., Zhang, Y., Meister, M., & Sanes, J. R. (2011). Age-related alterations in neurons of the mouse retina. Journal of Neuroscience, 31(44), 16033–16044.PubMedCentralCrossRefPubMed
Shi, Z., Birman, E., & Saragovi, H. U. (2007). Neurotrophic rationale in glaucoma: A TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cells in vivo. Developmental Neurobiology, 67(7), 884–894.CrossRefPubMed
Siliprandi, R., Canella, R., & Carmignoto, G. (1993). Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia. Investigative Ophthalmology & Visual Science, 34(12), 3232–3245.
Sivilia, S., Giuliani, A., Fernández, M., Turba, M. E., Forni, M., Massella, A., et al. (2009). Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat. BMC Neuroscience, 10, 52.PubMedCentralCrossRefPubMed
Skeie, J. M., Tsang, S. H., & Mahajan, V. B. (2011). Evisceration of mouse vitreous and retina for proteomic analyses. Journal of Visualized Experiments, 50, 2795.PubMed
Stranahan, A. M., Erion, J. R., & Wosiski-Kuhn, M. (2013). Reelin signaling in development, maintenance, and plasticity of neural networks. Ageing Research Reviews, 12(3), 815–822.PubMedCentralCrossRefPubMed
Tomomura, M., Rice, D. S., Morgan, J. I., & Yuzaki, M. (2001). Purification of Purkinje cells by fluorescence-activated cell sorting from transgenic mice that express green fluorescent protein. European Journal of Neuroscience, 14(1), 57–63.CrossRefPubMed
Topham, C. H., & Taylor, S. S. (2013). Mitosis and apoptosis: How is the balance set? Current Opinion in Cell Biology, 25(6), 780–785.CrossRefPubMed
Trotter, J. H., Klein, M., Jinwal, U. K., Abisambra, J. F., Dickey, C. A., Tharkur, J., et al. (2011). ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. Journal of Neuroscience, 31(40), 14413–14423.PubMedCentralCrossRefPubMed
Weng, S., Estevez, M. E., & Berson, D. M. (2013). Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones. PLoS One, 8, e66480.PubMedCentralCrossRefPubMed
Wexler, E. M., Berkovich, O., & Nawy, S. (1998). Role of the low-affinity NGF receptor (p75) in survival of retinal bipolar cells. Visual Neuroscience, 15(2), 211–218.CrossRefPubMed
Wilcox, R. R. (2002). Understanding the practical advantages of modern ANOVA methods. Journal of Clinical Child & Adolescent Psychology, 31(3), 399–412.CrossRef
Xu, J., Dodd, R. L., Makino, C. L., Simon, M. I., Baylor, D. A., & Chen, J. (1997). Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature, 389(6650), 505–509.CrossRefPubMed
Yamashita, T., Tucker, K. L., & Barde, Y. A. (1999). Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron, 24(3), 585–593.CrossRefPubMed
Metadata
Title
NGF Expression in Reelin-Deprived Retinal Cells: A Potential Neuroprotective Effect
Authors
Bijorn Omar Balzamino
Graziana Esposito
Ramona Marino
Flavio Keller
Alessandra Micera
Publication date
01-09-2015
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 3/2015
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-015-8360-z

Other articles of this Issue 3/2015

NeuroMolecular Medicine 3/2015 Go to the issue

Original Paper

KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population

Original Paper

Lower Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor Predicts Progression from Mild Cognitive Impairment to Alzheimer’s Disease

Original Paper

Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita

Review Paper

Structure, Distribution, and Function of Neuronal/Synaptic Spinules and Related Invaginating Projections

Original Paper

Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure

Original Paper

Restoration of Normal Cerebral Oxygen Consumption with Rapamycin Treatment in a Rat Model of Autism–Tuberous Sclerosis