Enhancing Experience-Dependent Plasticity Accelerates Vision Loss in a Murine Model of Retinitis Pigmentosa.

Abstract

PURPOSE: Retinitis pigmentosa (RP) causes retinal degeneration and the progressive loss of vision. Here, we evaluated whether enhancing experience-dependent plasticity prolongs vision in a mouse genetic model of autosomal dominant RP. METHODS: First, we quantified the loss of visual acuity under both mesopic and photopic conditions for mice heterozygous for the P23H mutation in the Rhodopsin gene (RhoP23H/+) and littermate controls. Then, we compared acuity to the magnitude of the b-wave measured from full-field electroretinograms (ffERG) or the response properties of excitatory neurons in layer 2/3 of primary visual cortex calculated from in vivo calcium imaging, under both mesopic and photopic conditions for each mouse. Last, we repeated these measurements and comparisons for mice that also lacked a functional gene for the Nogo-66 receptor (Ngr1), a gene required to close the critical period for visual plasticity. RESULTS: Acuity progressively declined under mesopic 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. Acuity deficits were more severe at earlier ages in Ngr1-/-;RhoP23H/+ mice, and no mice possessed sufficient acuity at 10 to 12 months of age to be tested on the visual water task. CONCLUSIONS: The RhoP23H/+ mouse model of RP displays progressive loss of visual acuity first under mesopic conditions and then under photopic conditions. The severity of acuity impairment correlates only broadly with deficits in retinal function measured with the ffERG but is consistent with the percentage of neurons in primary visual cortex responsive to higher spatial frequency visual stimuli measured with calcium imaging. Contrary to our hypothesis, enhancing neural plasticity is deleterious for visual function in RhoP23H/+ mice.