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Cone-Driven, Geniculocortical Responses in Canine Models of Outer Retinal Disease.
- Source :
-
Translational vision science & technology [Transl Vis Sci Technol] 2024 Jan 02; Vol. 13 (1), pp. 18. - Publication Year :
- 2024
-
Abstract
- Purpose: Canine models of inherited retinal degeneration are used for proof of concept of emerging gene and cell-based therapies that aim to produce functional restoration of cone-mediated vision. We examined functional magnetic resonance imaging (MRI) measures of the postretinal response to cone-directed stimulation in wild-type (WT) dogs, and in three different retinal disease models.<br />Methods: Temporal spectral modulation of a uniform field of light around a photopic background was used to target the canine L/M (hereafter "L") and S cones and rods. Stimuli were designed to separately target the postreceptoral luminance (L+S) and chrominance (L-S) pathways, the rods, and all photoreceptors jointly (light flux). These stimuli were presented to WT, and mutant PDE6B-RCD1, RPGR-XLPRA2, and NPHP5-CRD2 dogs during pupillometry and functional MRI (fMRI).<br />Results: Pupil responses in WT dogs to light flux, L+S, and rod-directed stimuli were consistent with responses being driven by cone signals alone. For WT animals, both luminance and chromatic (L-S) stimuli evoked fMRI responses in the lateral geniculate nucleus or visual cortex; RCD1 animals with predominant rod loss had similar responses. Responses to cone-directed stimulation were reduced in XLPRA2 and absent in CRD2. NPHP5 gene augmentation restored the cortical response to luminance stimulation in a CRD2 animal.<br />Conclusions: Cone-directed stimulation during fMRI can be used to measure the integrity of luminance and chrominance responses in the dog visual system. The NPHP5-CRD2 model is appealing for studies of recovered cone function.<br />Translational Relevance: fMRI assessment of cone-driven cortical response provides a tool to translate cell/gene therapies for vision restoration.
Details
- Language :
- English
- ISSN :
- 2164-2591
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Translational vision science & technology
- Publication Type :
- Academic Journal
- Accession number :
- 38241039
- Full Text :
- https://doi.org/10.1167/tvst.13.1.18