Preservation of vision by transpalpebral electrical stimulation in mice with inherited retinal degeneration.

Introduction: The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice (Rho -/- ), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in Rho -/- mice. Methods: To elucidate the impact of electrical stimulation on cone survival, Rho -/- mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100 µA amplitude, starting at six weeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of Rho -/- mice. The sham group received daily treatments without the application of ES. Results: Our study revealed significant improvement of visual function in Rho -/- mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments. Discussion: This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa.

[Long time survival of the regenerated optic nerve axons in Bcl-2 transgenic mice].

OBJECTIVE: To study if the regenerating axons can be alive till adult and restore function when the optic nerve was crushed at 3 days after birth (P3) in Bcl-2 transgenic mice. METHODS: It was a experimental study. Optic nerve crush was performed on C57Bl/6J and Bcl-2 transgenic mice at P3, immediately followed by intro vitreous injection of a nerve axon tracer--cholera toxin B subunit conjugated with fluorescein (CTB-F). Mice were sacrificed at day 4, 8, 10, 13, 18 and 24 post operation, the optic nerve and the brain was cryosectioned. Immunofluorescence staining of GAP43 was carried out to evaluate the regenerating axon. Same procedure was used together with immediately MK801 intro vitreous injection, gel foam soaked with NMDA or BDNF put in superior colliculus. Mice were sacrificed on 10 or 13 days post operation. Optic nerve regeneration was evaluated. RESULTS: The regenerated optic nerve axons reached the targets in the brain at 4 days post operation. But after 10 days, the regenerated axons were retracted. MK801, NMDA and BDNF can prolonged the alive of regenerated axons in the brain targets, but its alive was only lasted 3 more days. It retracted finally on 13 days after surgery. CONCLUSION: Optic nerve can regenerate successfully to reach the targets in the brain when it was crushed on P3 in Bcl-2 transgenic mice, but the regenerated nerve axons can only survive for 10 days when it is retracted from the brain. It is probably because of the failure of the synapse formation at this time.