Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage
In addition to its role as an endocrine messenger, growth hormone (GH) also acts as a neurotrophic factor in the central nervous system (CNS), whose effects are involved in neuroprotection, axonal growth, and synaptogenic modulation. An increasing amount of clinical evidence shows a beneficial effec...
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MDPI AG
2019-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/18/4433 |
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| author | Carlos G. Martinez-Moreno David Epardo Jerusa E. Balderas-Márquez Thomas Fleming Martha Carranza Maricela Luna Steve Harvey Carlos Arámburo |
| author_facet | Carlos G. Martinez-Moreno David Epardo Jerusa E. Balderas-Márquez Thomas Fleming Martha Carranza Maricela Luna Steve Harvey Carlos Arámburo |
| author_sort | Carlos G. Martinez-Moreno |
| collection | DOAJ |
| description | In addition to its role as an endocrine messenger, growth hormone (GH) also acts as a neurotrophic factor in the central nervous system (CNS), whose effects are involved in neuroprotection, axonal growth, and synaptogenic modulation. An increasing amount of clinical evidence shows a beneficial effect of GH treatment in patients with brain trauma, stroke, spinal cord injury, impaired cognitive function, and neurodegenerative processes. In response to injury, Müller cells transdifferentiate into neural progenitors and proliferate, which constitutes an early regenerative process in the chicken retina. In this work, we studied the long-term protective effect of GH after causing severe excitotoxic damage in the retina. Thus, an acute neural injury was induced via the intravitreal injection of kainic acid (KA, 20 µg), which was followed by chronic administration of GH (10 injections [300 ng] over 21 days). Damage provoked a severe disruption of several retinal layers. However, in KA-damaged retinas treated with GH, we observed a significant restoration of the inner plexiform layer (IPL, 2.4-fold) and inner nuclear layer (INL, 1.5-fold) thickness and a general improvement of the retinal structure. In addition, we also observed an increase in the expression of several genes involved in important regenerative pathways, including: synaptogenic markers (DLG1, NRXN1, GAP43); glutamate receptor subunits (NR1 and GRIK4); pro-survival factors (BDNF, Bcl-2 and TNF-R2); and Notch signaling proteins (Notch1 and Hes5). Interestingly, Müller cell transdifferentiation markers (Sox2 and FGF2) were upregulated by this long-term chronic GH treatment. These results are consistent with a significant increase in the number of BrdU-positive cells observed in the KA-damaged retina, which was induced by GH administration. Our data suggest that GH is able to facilitate the early proliferative response of the injured retina and enhance the regeneration of neurite interconnections. |
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| spelling | doaj.art-a4d350dd9a53465d9ab6f0ed162986b72022-12-22T03:41:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-09-012018443310.3390/ijms20184433ijms20184433Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic DamageCarlos G. Martinez-Moreno0David Epardo1Jerusa E. Balderas-Márquez2Thomas Fleming3Martha Carranza4Maricela Luna5Steve Harvey6Carlos Arámburo7Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoDepartment of Physiology, University of Alberta, Edmonton, AB T6G 2H7, CanadaDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, MexicoIn addition to its role as an endocrine messenger, growth hormone (GH) also acts as a neurotrophic factor in the central nervous system (CNS), whose effects are involved in neuroprotection, axonal growth, and synaptogenic modulation. An increasing amount of clinical evidence shows a beneficial effect of GH treatment in patients with brain trauma, stroke, spinal cord injury, impaired cognitive function, and neurodegenerative processes. In response to injury, Müller cells transdifferentiate into neural progenitors and proliferate, which constitutes an early regenerative process in the chicken retina. In this work, we studied the long-term protective effect of GH after causing severe excitotoxic damage in the retina. Thus, an acute neural injury was induced via the intravitreal injection of kainic acid (KA, 20 µg), which was followed by chronic administration of GH (10 injections [300 ng] over 21 days). Damage provoked a severe disruption of several retinal layers. However, in KA-damaged retinas treated with GH, we observed a significant restoration of the inner plexiform layer (IPL, 2.4-fold) and inner nuclear layer (INL, 1.5-fold) thickness and a general improvement of the retinal structure. In addition, we also observed an increase in the expression of several genes involved in important regenerative pathways, including: synaptogenic markers (DLG1, NRXN1, GAP43); glutamate receptor subunits (NR1 and GRIK4); pro-survival factors (BDNF, Bcl-2 and TNF-R2); and Notch signaling proteins (Notch1 and Hes5). Interestingly, Müller cell transdifferentiation markers (Sox2 and FGF2) were upregulated by this long-term chronic GH treatment. These results are consistent with a significant increase in the number of BrdU-positive cells observed in the KA-damaged retina, which was induced by GH administration. Our data suggest that GH is able to facilitate the early proliferative response of the injured retina and enhance the regeneration of neurite interconnections.https://www.mdpi.com/1422-0067/20/18/4433growth hormoneretinaregenerationsynaptogenicneurotrophicexcitotoxicity |
| spellingShingle | Carlos G. Martinez-Moreno David Epardo Jerusa E. Balderas-Márquez Thomas Fleming Martha Carranza Maricela Luna Steve Harvey Carlos Arámburo Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage International Journal of Molecular Sciences growth hormone retina regeneration synaptogenic neurotrophic excitotoxicity |
| title | Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage |
| title_full | Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage |
| title_fullStr | Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage |
| title_full_unstemmed | Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage |
| title_short | Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage |
| title_sort | regenerative effect of growth hormone gh in the retina after kainic acid excitotoxic damage |
| topic | growth hormone retina regeneration synaptogenic neurotrophic excitotoxicity |
| url | https://www.mdpi.com/1422-0067/20/18/4433 |
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