Research Overview

Optic nerve regeneration has been studied by Dr. Benowitz lab for numbers of years. The lab has shown that a trophic factor secreted by inflammatory cells, named oncomodulin, can induce axon regeneration. The combination of this trophic factor together with the deletion of a gene that suppresses cell growth and protein synthesis, the pten gene, showed a synergistic effect on axon growth after a lesion to the optic nerve. Another study investigated the long-term regeneration of retinal ganglion cells (RGCs) using a combination of treatments with the aim of increasing the levels of oncomodulin intraocularly, through a controlled inflammation, and also increase the levels of cAMP, which is involved in the binding of oncomodulin to its receptor, together with deletion of PTEN. This treatment enabled RGCs to extend their axons through the full-length of the optic nerve, enter the brain, and make connections with the main visual targets, furthermore recover of simple visual reflexes was also achieved. After this study one important question to be addressed was whether regenerating axons can become myelinated and recover the electrical domains present in nodes of Ranvier and paranodal regions. In a study together with the laboratory of Dr. Mathew Rasband – Baylor College of Medicine, Houston – was shown that after injury axons dismantle these electrical domains in the nodal and paranodal regions, furthermore axons also lose their myelin. After the combinatorial treatment RGCs’ axons reassemble these domains and become myelinated different from animals that no treatment was given, they showed no recovery of those domains.

About the Researcher

Silmara de Lima has been investigating regeneration of axons in the central nervous system (CNS) since 2007 when she started her Master in Brazil, and pursued this topic during her PhD training as well, which was begun in Brazil and continued at Boston Children’s Hospital/Harvard Medical School. Dr. Larry Benowitz, one of the leaders in the field of optic nerve regeneration, was her mentor for the major part of her PhD training. In 2012, they published a paper showing that a combinatorial treatment enabled retinal ganglion cells (RGCs) to regenerate injured axons the entire length of the optic nerve, and find their way back to central target areas, become remyelinated, and help restore simple visual responses. Recently, they discovered that regenerating axons can become myelinated and reassemble important domains that are responsible for the propagation of action potential, the signal that travels from the retina to the visual targets in the brain. Currently, she is working on methods for detecting regenerated axons in the optic nerve using electron microscopy. And, continuing the study on myelination of regenerating axons.

Researcher Services

Researcher Areas

  • Myelination
  • Optic nerve regeneration

Research Departments

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Researcher Centers

PUBLICATIONS

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  1. Ramalho BDS, Almeida FM, Sales CM, de Lima S, Martinez AMB. Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice. Neural Regen Res. 2018 Jun; 13(6):1046-1053. View abstract
  2. Li Y, Andereggen L, Yuki K, Omura K, Yin Y, Gilbert HY, Erdogan B, Asdourian MS, Shrock C, de Lima S, Apfel UP, Zhuo Y, Hershfinkel M, Lippard SJ, Rosenberg PA, Benowitz L. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration. Proc Natl Acad Sci U S A. 2017 01 10; 114(2):E209-E218. View abstract
  3. de Lima S, Mendonça HR, Goulart CO, Martinez AM. Past, present and future of preserving and restoring function in the visual system: removing galectin-3 as a promising treatment. Neural Regen Res. 2017 Jan; 12(1):58-59. View abstract
  4. Marin MA, de Lima S, Gilbert HY, Giger RJ, Benowitz L, Rasband MN. Reassembly of Excitable Domains after CNS Axon Regeneration. J Neurosci. 2016 08 31; 36(35):9148-60. View abstract
  5. Goulart CO, Jürgensen S, Souto A, Oliveira JT, de Lima S, Tonda-Turo C, Marques SA, de Almeida FM, Martinez AM. A combination of Schwann-cell grafts and aerobic exercise enhances sciatic nerve regeneration. PLoS One. 2014; 9(10):e110090. View abstract
  6. Koriyama Y, Kurimoto T, de Lima S, Benowitz L. [Reinnervation of central visual areas and recovery of visual functions following optic nerve regeneration in adult mice]. Brain Nerve. 2014 Mar; 66(3):265-72. View abstract
  7. Oliveira JT, Mostacada K, de Lima S, Martinez AM. Bone marrow mesenchymal stem cell transplantation for improving nerve regeneration. Int Rev Neurobiol. 2013; 108:59-77. View abstract
  8. de Lima S, Koriyama Y, Kurimoto T, Oliveira JT, Yin Y, Li Y, Gilbert HY, Fagiolini M, Martinez AM, Benowitz L. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc Natl Acad Sci U S A. 2012 Jun 05; 109(23):9149-54. View abstract
  9. de Lima S, Habboub G, Benowitz LI. Combinatorial therapy stimulates long-distance regeneration, target reinnervation, and partial recovery of vision after optic nerve injury in mice. Int Rev Neurobiol. 2012; 106:153-72. View abstract