Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats

• Type of Material: Article
• Authors: Adam M. Hanif, Emory University; Moon K. Kim, Emory University; Joel G. Thomas, University of Illinois at Chicago; Vincent Ciavatta, Emory University; Micah Chrenek, Emory University; John R. Hetling, University of Illinois at Chicago; Machelle Pardue, Emory University
• Language: English
• Date: 2016-08
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier B.V. or its licensors or contributors.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2016.06.010
• Title of Journal or Parent Work: Experimental Eye Research
• ISSN: 0014-4835
• Volume: 149
• Start Page: 75
• End Page: 83
• Grant/Funding Information: This work was supported by Merit Review Award C4761R and a Research Career Scientist Award (MTP; C9257S) from the United States Department of Veterans Affairs, Rehabilitation Research and Development Service; a P30 EY006360 from the National Institute of Health, National Eye Institute; and a Departmental award to the Emory Eye Center from Research to Prevent Blindness.
• Keywords: Retinal degeneration; PHOTORECEPTOR DEGENERATION; Electrical stimulation therapy; ALTERNATING-CURRENT STIMULATION; OPTIC-NERVE DAMAGE; DIELECTRIC-PROPERTIES; MULLER CELLS; Neuroprotection; Retinitis pigmentosa; Science & Technology; Ophthalmology; DARK-ADAPTED ELECTRORETINOGRAM; B-WAVE; RETINITIS-PIGMENTOSA; GLUTAMINE-SYNTHETASE; RETINAL GANGLION-CELLS; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Opthamology; Biology, Neuroscience

Abstract

Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30 min of low-level electrical stimulation (4 μA at 5 Hz; n = 10) or sham stimulation (Sham group; n = 15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30 min, and retinal tissue harvested at 1 h and 24 h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1 h, but not 24 h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.