Cone-mediated encoding of natural stimuli is robust in Cngb1 mouse model of advanced retinitis pigmentosa

Abstract

Purpose : Retinitis pigmentosa (RP) is an inherited blinding disease that causes degeneration of rod photoreceptors. Rod death causes many second-order changes in retinal circuits including the remodeling of bipolar cell dendrites and cone death. For treating vision loss from RP, a critical issue is determining how the fidelity of cone-mediated visual signaling depends on the amount of rod death.

Methods : We measured responses of retinal ganglion cells (RGCs) to artificial and natural visual stimuli under mesopic and photopic conditions using a mouse model of Cngb1-RP. In this model, rod death is a relatively slow process: rods progressively die until all are lost at 6-7 months. We measured RGC responses in animals at 1 month intervals from 1-7 months and compared responses to RGCs from WT mice. Ex vivo retinal recordings were performed using a 512 electrode array. Retina were placed RGC side down on the array, spikes were identified and sorted while presenting visual stimuli to the photoreceptors. The fidelity of signaling was examined in two ways. First, checkerboard noise was used to estimate the spatial and temporal receptive fields (RFs) of the RGCs. Second, repeated sequences of checkerboard noise or a natural movie were presented. These two approaches allowed an examination of the visual features encoded by the RGCs and the fidelity of this encoding process.

Results : Under both mesopic and photopic conditions, RF structure was relatively robust to the loss of rods out to 6 months of age (<10% rods surviving). Despite this relative stability in RF structure, the fidelity of visual signaling, measured by the mutual information (MI) between stimulus and response, was strongly impacted by rod loss. MI rates under mesopic conditions rapidly deteriorated when 50-80% of the rods remained. Under photopic conditions, MI rates were higher and less impacted by rod loss. Surprisingly, MI rates to natural movies were minimally impacted by rod loss and did not deteriorate significantly until after nearly all rods were lost and cones began to die.

Conclusions : Our results indicate that cone-mediated signaling of natural stimuli are minimally impacted by rod loss. This indicates that therapies for RP are likely to result in useful cone-mediated vision so long as rod photoreceptor death is halted.

This is a 2021 ARVO Annual Meeting abstract.