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

Cecilia A Attaway ^1,2, Thomas C Brown ^1,3, Maureen A McCall ^1,2

⁰Department of Anatomical Sciences and Neurobiology, School of Medicine; University of Louisville, Louisville, KY, 40202.

Biorxiv : the Preprint Server for Biology +

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September 15, 2025

View abstract on PubMed

Summary

Enhancing neural plasticity did not preserve vision in a retinitis pigmentosa mouse model. Instead, deleting the nogo-66 receptor gene accelerated vision loss, showing plasticity enhancement can be detrimental in neurodegeneration.

Area Of Science

Neuroscience
Ophthalmology
Genetics

Background

Neural plasticity modulation is a therapeutic strategy for neurologic disorders.
Retinitis pigmentosa (RP) is a group of inherited diseases that cause progressive vision loss.
The P23H mutation in the Rhodopsin gene is a common cause of RP.

Purpose Of The Study

To investigate if enhancing experience-dependent plasticity can prolong vision in a murine model of RP.
To determine the relationship between visual acuity deficits and neural responses in RP.

Main Methods

Quantified visual acuity loss in scotopic and photopic conditions in P23H heterozygous mice.
Assessed retinal response using electroretinogram.
Measured the percentage of cortical excitatory layer 2/3 neurons responsive to visual stimuli.
Deleted the nogo-66 receptor gene (Ngr1) to enhance plasticity in P23H heterozygous mice.

Main Results

Visual acuity progressively declined in P23H/+ mice under scotopic and photopic conditions.
Acuity deficits correlated with reduced cortical neuron responsiveness, not solely retinal response.
Deleting Ngr1 accelerated vision loss in P23H/+ mice, indicating enhanced plasticity was maladaptive.

Conclusions

Enhancing neural plasticity can be detrimental in the context of neurodegenerative diseases like RP.
Targeting plasticity needs careful consideration in therapeutic strategies for vision loss.