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Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage

Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230, Mexico
Department of Physiology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Authors to whom correspondence should be addressed.
Authors equally contributed to this work.
Int. J. Mol. Sci. 2019, 20(18), 4433;
Received: 12 August 2019 / Revised: 3 September 2019 / Accepted: 4 September 2019 / Published: 10 September 2019
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. View Full-Text
Keywords: growth hormone; retina; regeneration; synaptogenic; neurotrophic; excitotoxicity growth hormone; retina; regeneration; synaptogenic; neurotrophic; excitotoxicity
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MDPI and ACS Style

Martinez-Moreno, C.G.; Epardo, D.; Balderas-Márquez, J.E.; Fleming, T.; Carranza, M.; Luna, M.; Harvey, S.; Arámburo, C. Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage. Int. J. Mol. Sci. 2019, 20, 4433.

AMA Style

Martinez-Moreno CG, Epardo D, Balderas-Márquez JE, Fleming T, Carranza M, Luna M, Harvey S, Arámburo C. Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage. International Journal of Molecular Sciences. 2019; 20(18):4433.

Chicago/Turabian Style

Martinez-Moreno, Carlos G., David Epardo, Jerusa E. Balderas-Márquez, Thomas Fleming, Martha Carranza, Maricela Luna, Steve Harvey, and Carlos Arámburo. 2019. "Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage" International Journal of Molecular Sciences 20, no. 18: 4433.

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