Enhancing experience-dependent plasticity accelerates vision loss in a murine model of retinitis pigmentosa

Abstract

Modulating neural plasticity is pursued as a therapeutic approach for several neurologic conditions. Here we evaluated if enhancing experience-dependent plasticity prolongs vision in a murine model of retinitis pigmentosa. First, we quantified the loss of visual acuity under both scotopic and photopic conditions for mice heterozygous for the P23H mutation in the Rhodopsin gene (Rho P23H/+). Acuity progressively declined under scotopic conditions followed by photopic conditions. Acuity deficits only broadly correlated with the retinal response measured by the electroretinogram. In contrast, acuity deficits were consistent with the percent of cortical excitatory layer 2/3 neurons responsive to higher spatial frequency visual stimuli. Then, we tested if enhancing plasticity in adult visual circuity by deleting the nogo-66 receptor gene (Ngr1) would preserve vision in Rho P23H/+ mice. However, loss of vision was accelerated in Ngr1 -/-; Rho P23H/+ mice. Thus, enhancing plasticity can be maladaptive in the context of neural degeneration.