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Transcorneal Electrical Stimulation Reduces Neurodegenerative Process in a Mouse Model of Glaucoma

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Abstract

Glaucoma is a neurodegenerative disease in which the retinal ganglion cell axons of the optic nerve degenerate concomitant with synaptic changes in the retina, leading finally to death of the retinal ganglion cells (RGCs). Electrical stimulation has been used to improve neural regeneration in a variety of systems, including in diseases of the retina. Therefore, the focus of this study was to investigate whether transcorneal electrical stimulation (TES) in the DBA2/J mouse model of glaucoma could improve retinal or optic nerve pathology and serve as a minimally invasive treatment option. Mice (10 months-old) received 21 sessions of TES over 8 weeks, after which we evaluated RGC number, axon number, and anterograde axonal transport using histology and immunohistochemistry. To gain insight into the mechanism of proposed protection, we also evaluated inflammation by quantifying CD3+ T-cells and Iba1+ microglia; perturbations in metabolism were shown via the ratio pAMPK to AMPK, and changes in trophic support were tested using protein capillary electrophoresis. We found that TES resulted in RGC axon protection, a reduction in inflammatory cells and their activation, improved energy homeostasis, and a reduction of the cell death-associated p75NTR. Collectively, the data indicated that TES maintained axons, decreased inflammation, and increased trophic factor support, in the form of receptor presence and energy homeostasis, suggesting that electrical stimulation impacts several facets of the neurodegenerative process in glaucoma.

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Acknowledgments

The authors would like to thank Amelia McMullen, Colin Waltz, and Tyree Lewis for colony support, and Josephine Lepp, Lucy Coughlin, and Ryan Zubricky for technical assistance. This work was supported by NIH EY026662 (DMI). We also thank the generous support through the Margaret F. Donovan Endowed Chair for Women in Engineering at the University of Akron.

Author Contributions

Jassim, Cavanaugh, and Stukel, performed the experiments; Jassim and Cavanaugh undertook data analysis and writing. Willits and Inman conceived the experiments, supported data analysis, interpretation, and writing.

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Author notes

  1. Rebecca Willits

    Present address: Department of Chemical Engineering, Northeastern University, Boston, MA, USA

  2. Denise M. Inman

    Present address: North Texas Eye Research Institute, UNT-HSC, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA

  3. Assraa Hassan Jassim

    Present address: Department of Basic and Translational Sciences, University of Pennsylvania, Philadelphia, PA, USA

  4. Assraa Hassan Jassim and McKay Cavanaugh have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA

    Assraa Hassan Jassim & Denise M. Inman

  2. Department of Biomedical Engineering, University of Akron, Akron, OH, USA

    McKay Cavanaugh, Jessica Stukel Shah & Rebecca Willits

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  1. Assraa Hassan Jassim
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Correspondence to Rebecca Willits or Denise M. Inman.

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Associate Editor Joel D. Stitzel oversaw the review of this article.

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Jassim, A.H., Cavanaugh, M., Shah, J.S. et al. Transcorneal Electrical Stimulation Reduces Neurodegenerative Process in a Mouse Model of Glaucoma. Ann Biomed Eng 49, 858–870 (2021). https://doi.org/10.1007/s10439-020-02608-8

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