Expression of Trk, Neurotrophin Receptors in Dog Retina After Electrical Stimulation

Abstract

Abstract: : Purpose: Cell depolarization induced by electrical stimulation may potentiate neural protection/regeneration activity mediated by neurotrophins (NTs). NTs exert their biological actions by binding to their cognate tyrosine kinase (trk) receptors, including TrkA, TrkB, and TrkC. The purpose of this study is to determine the effects of electrical stimulation on the distribution of Trk expression in normal dog retina. Methods: Three normal adult dogs were used. An electrical stimulus, with a charge density of 0.35–1 mC/cm2, was applied to the epiretinal surface for four hours. The dogs were followed up for one month before sacrifice. Retinal tissue was fixed with 10% formalin and processed for paraffin section. The distribution of TrkA, TrkB, and TrkC expression in the retina of normal stimulated dogs and a non–stimulated dog was studied using immunohistochemistry. Results: TrkC immunoreactivity was detected in the majority of retinal ganglion cells (RGCs) and optic nerve fibers in the retina after electrical stimulation, but not in the control non–stimulated retina. Focal Trk C immunoreactivity was also seen in the inner nuclear layer and inner plexiform layer in stimulated retina. The expression of TrkB was similar to TrkC in the distribution of immunoreactivity but weaker than TrkC in stimulated retina. No TrKA immunoreactivity was detected in either stimulated or non–stimulated retina. Conclusions: Eyes that were implanted and stimulated for 4 hours showed an increased expression of TrkB and TrkC, neurotrophin receptors on RGCs and their axons. This suggests that the Trk signaling pathway was involved in the electrical stimulation induced tissue responses. (Supported by NIH–NEI grants 1R24EY12893, NIH EY03040, Research to Prevent Blindness, and Fletcher Jones Foundation)

Keywords: regeneration • neuroprotection • retina