Electrically Evoked Potentials Are Reduced Compared to Axon Numbers in Rhodopsin P347L Transgenic Rabbits With Severe Photoreceptor Degeneration

Abstract

PURPOSE. To determine the relationship between the amplitudes of the electrically evoked potentials (EEPs) and the number of optic nerve axons at a late stage of retinal degeneration in rhodopsin P347L transgenic (Tg) rabbits, a model of retinitis pigmentosa. METHODS. Six eyes of six wild-type (WT) (43.8 6 7.5 months of age) and six eyes of six Tg (40.3 6 2.6 months of age) rabbits were studied. The EEPs were elicited by 1 to 5 mA of transcorneal electrical stimulation. The first positive wave, the P1 component, was analyzed. After euthanasia, the number of axons in the optic nerve was counted. RESULTS. The threshold current to elicit a P1 was significantly higher in Tg rabbits than WT rabbits. The amplitude of P1 elicited by 5 mA in Tg rabbits was about 24% of that in WT rabbits (P < 0.01). The number of axons in the optic nerve of Tg rabbits was reduced to about 59% of that of WT rabbits (P < 0.01). The correlation between the axon number and the amplitude of the P1 in Tg and WT rabbits was not significant. The mean ratio of the P1 amplitude/axon in Tg rabbits was decreased to 53% of that in WT rabbits (P < 0.05). CONCLUSIONS. The degree of reduction in the EEP in Tg rabbits is more severe than the reduction in the number of optic nerve axons. The use of transcorneal electrical stimulation to determine the suitable candidates for prosthesis at the end-stage of retinitis pigmentosa may underestimate the condition of the optic nerves.

Gene Editing in Rabbits: Unique Opportunities for Translational Biomedical Research

“…However, most of these rabbit models were induced experimentally, which limited their application in hereditary eye diseases. Due to the lack of a technology to generate targeted gene modifications in rabbits, for many years, genetically modified rabbit models for ocular disease studies were restricted to transgenic rabbits only (Kondo et al, 2009;Yokoyama et al, 2010;Hirota et al, 2012;Ueno et al, 2013Ueno et al, , 2019Asakawa et al, 2015Asakawa et al, , 2016Nagai et al, 2016;Nakagami et al, 2016;Kominami et al, 2017Kominami et al, , 2019Okado et al, 2017;Roy et al, 2019).…”

USH2A gene mutations in rabbits lead to progressive retinal degeneration and hearing loss

“…Rabbits, compared with mice, are closer to humans in terms of phylogenesis, anatomical features, physiology, and pathophysiological responses [10][11][12][13][14] , and are used as a classic lab animal species to develop novel therapeutics for humans and refine medical and surgical equipment 13,[15][16][17][18][19] . Historically, retinal degeneration has been studied in rhodopsin Pro347Leu transgenic rabbits, a model of RP [20][21][22][23][24][25][26][27][28][29][30][31] . Recently, the emerging gene editing technology in rabbits has greatly increased their value to biomedicine, motivating our efforts to develop rabbits that carry the disease causing mutations found in human patients, as models to replicate human diseases more precisely [32][33][34] .…”

Simulation-Based Designing of Suitable Stimulation Factors for Presenting Two Phosphenes Simultaneously to Lower Side of Field of View

“…Various noninvasive methods have been studied for eye stimulation methods. tACS (transcranial alternating current stimulation) [ 5 ], which places electrodes on the skin, TES (transcorneal electrical stimulation) [ 6 ], which places contact-lens-shaped electrodes on the cornea of the eye, and TpES (transpalpebral electrical stimulation) [ 7 , 8 ], which places electrodes on the eyelids, have been reported. It has also been suggested that stimulating the eyeball may lead to the treatment of retinitis pigmentosa and optic neuropathy [ 8 , 9 ].…”