Abstract
Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cells expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed this issue in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network, reminiscent of the neurodevelopmental state, and potentiation of rod - rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. These results suggest retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.
Highlights
Neurons and neuronal networks require mechanisms for maintaining their stability in the face of numerous perturbations occurring over a lifetime
Retinal remodeling following photoreceptor cell death has been observed in a number of genetic and induced animal models of retinal degeneration (Beltran, 2009; Chang, Hawes, Davisson, & Heckenlively, 2007; LaVail et al, 2018; Petersen-Jones, 1998; Ross et al, 2012), as well as in post mortem human eye specimens from patients with Retinitis Pigmentosa (RP) or Age-related Macular Degeneration (AMD) (Fariss et al, 2000; Jones, Pfeiffer, Ferrell, Watt, Marmor, et al, 2016; Jones, Pfeiffer, Ferrell, Watt, Tucker, et al, 2016; Li, Kljavin, & Milam, 1995)
We found 20 %, 60 % and 73 % decreases in central retinal outer nuclear layer (ONL) thickness at 1, 3- and 5-months of age, respectively, in P23H mice compared to WT littermates (Figure 1H)
Summary
Neurons and neuronal networks require mechanisms for maintaining their stability in the face of numerous perturbations occurring over a lifetime. Homeostatic plasticity refers to the process whereby the activity of the neuron or neuronal network is maintained Binocular visual deprivation triggers compensatory synaptic changes in the primary visual cortex leading to the stabilization of spiking activity (Desai, Cudmore, Nelson, & Turrigiano, 2002; Goel et al, 2006; Goel & Lee, 2007), and stroke can trigger homeostatic plasticity that is thought to compensate for neuronal damage, which plays an important role in early phase rehabilitation (Murphy & Corbett, 2009). Homeostatic plasticity counteracts insufficient activity in neural synapses Homeostatic plasticity counteracts insufficient activity in neural synapses (Burrone & Murthy, 2003; G. Turrigiano, 2012), but it works to prevent saturation of synapses that could be caused by positive feedback mediated by Hebbian plasticity, which is better known for its role in experience-dependent plasticity, learning and memory (Abraham & Bear, 1996)
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