Chronic Intravitreous Infusion of Ciliary Neurotrophic Factor Modulates Electrical Retinal Stimulation Thresholds in the RCS Rat

Abstract

Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Phosphene Thresholds Elicited by Transcorneal Electrical Stimulation in Healthy Subjects and Patients with Retinal Diseases

“…[35][36][37] In animal experiments electrical stimulation has been shown to be beneficial for the survival of photoreceptors in Royal College of Surgeon's (RCS) rats, 38 to rescue ganglion cells after optic nerve injury 39,40 and to preserve retinal cells after light-induced retinal damage (Zhang H, et al IOVS 2009;50:ARVO E-Abstract 3615). 41 The neuroprotective effects of electrical stimulation have been attributed to upregulation of growth factors, such as insulin-like growth factor-1 (IGF-1), 39,42 fibroblast growth factor-2 (FGF-2), 34,43 ciliary neurotrophic factor (CNTF), 44,45 brain-derived neurotrophic factor (BDNF), 41,46 and to overexpression of neuroprotective genes, such as B-cell lymphoma-2 (BCL-2), 47 BAX, or some tumor necrosis factor genes.…”

Update on emerging drugs for sarcopenia – age-related muscle wasting

“…NTC-201, an intravitreal implant developed by Neurotech that delivered CNTF using ECT, was effective in a canine model of retinitis pigmentosa and, in human trials, protecting the retina from degeneration [78][79][80][81] . It should be noted that sustained CNTF expression from subretinal injection of a recombinant adeno-associated virus expressing CNTF in transgenic mice with a mutation found in human retinitis pigmentosa resulted in altered photoreceptor profiles and disorganisation of retinal cells, leading the investigator to conclude that strict regulation of CNTF may be required for its therapeutic application for preventing retinal degeneration [82] .…”

GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins

“…According to the results from previous experiments, there are several lines of evidence that the death of photoreceptors can be delayed with cytokines, neurotrophic or neuroprotective factors [29][30][31][32][33][34][35][36][37][38][39]. To this end, apoptotic cascades can be blocked either directly through receptor-mediated signalling, typical for neurotrophic factor or growth factors [40], or indirectly through molecules produced by glial cells.…”