Visual Cortex Engagement in Retinitis Pigmentosa.

Gianluca Pietra,Laura Baroncelli,Lucia Galli,Tiziana Bonifacino,Davide Talamonti,Giambattista Bonanno,Alessandro Sale

doi:10.3390/ijms22179412

Abstract

Retinitis pigmentosa (RP) is a family of inherited disorders caused by the progressive degeneration of retinal photoreceptors. There is no cure for RP, but recent research advances have provided promising results from many clinical trials. All these therapeutic strategies are focused on preserving existing photoreceptors or substituting light-responsive elements. Vision recovery, however, strongly relies on the anatomical and functional integrity of the visual system beyond photoreceptors. Although the retinal structure and optic pathway are substantially preserved at least in early stages of RP, studies describing the visual cortex status are missing. Using a well-established mouse model of RP, we analyzed the response of visual cortical circuits to the progressive degeneration of photoreceptors. We demonstrated that the visual cortex goes through a transient and previously undescribed alteration in the local excitation/inhibition balance, with a net shift towards increased intracortical inhibition leading to improved filtering and decoding of corrupted visual inputs. These results suggest a compensatory action of the visual cortex that increases the range of residual visual sensitivity in RP.

Highlights

Retinitis pigmentosa (RP) is a group of rare, inherited disorders involving the progressive breakdown and loss of retinal photoreceptors
We found that the visual cortex undergoes a significant alteration of the intracortical excitation/inhibition balance alongside photoreceptor degeneration and that antagonizing GABAergic neurotransmission further deteriorates visual functions
It is well known that the balance between excitatory and inhibitory neurotransmission is a key regulator of visual cortex plasticity and the brain’s capability to fine-tune to the input salient features [36,37,38,39,40]

Summary

Introduction

Retinitis pigmentosa (RP) is a group of rare, inherited disorders involving the progressive breakdown and loss of retinal photoreceptors. Genetic mutations responsible for RP produce biochemical defects in multiple pathways, but the common result is the degeneration of rod and cone photoreceptors, which causes loss of night vision, gradual narrowing of the visual field, dyschromatopsia, and eventually a decline in visual acuity [1,2]. While there are no effective treatments for RP, recent research is focusing on novel therapeutic strategies, including pharmacological targeting, gene augmentation therapy, cell transplants, and electronic prosthesis, aimed at preventing photoreceptor degeneration or replacing light-responsive parts of the retina [4,5,6,7,8,9,10] These avenues are promising for vision recovery and/or preservation in RP patients [2], the integrity of the visual system beyond the photoreceptor layer is a crucial constraint for the success of any retinal treatment. The ability to evoke phosphenes is reduced in RP patients, in subjects with a high level of visual deafferentation [23,24,25,26]

Methods

Results

Conclusion