Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy
Retinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a second...
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doaj-9c677e2c44b64f56a05c7b12e950a5372020-11-25T02:58:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-01216055605510.3390/ijms21176055Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone DystrophyMark M. Hassall0Michelle E. McClements1Alun R. Barnard2Maria í. Patricio3Sher A. Aslam4Robert E. Maclaren5Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKRetinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a secondary degeneration. Changes in the gene expression profile of cone photoreceptor cells are likely to occur prior to observable physiological changes. To this end, we sought to achieve greater understanding of the changes in cone photoreceptor cells early in the degeneration process of the <i>Rho<sup>−/−</sup></i>mouse model. To account for gene expression changes attributed to loss of cone photoreceptor cells, we normalized PCR in the remaining number of cones to a cone cell reporter (<i>OPN1-GFP</i>). Gene expression profiles of key components involved in the cone phototransduction cascade were correlated with tests of retinal cone function prior to cell loss. A significant downregulation of the photoreceptor transcription factor <i>Crx</i> was observed, which preceded a significant downregulation in cone opsin transcripts that coincided with declining cone function. Our data add to the growing understanding of molecular changes that occur prior to cone dysfunction in a model of rod-cone dystrophy. It is of interest that gene supplementation of <i>CRX</i> by adeno-associated viral vector delivery prior to cone cell loss did not prevent cone photoreceptor degeneration in this mouse model.https://www.mdpi.com/1422-0067/21/17/6055retinacone photoreceptorsretinitis pigmentosarod-cone dystrophygene therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mark M. Hassall Michelle E. McClements Alun R. Barnard Maria í. Patricio Sher A. Aslam Robert E. Maclaren |
spellingShingle |
Mark M. Hassall Michelle E. McClements Alun R. Barnard Maria í. Patricio Sher A. Aslam Robert E. Maclaren Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy International Journal of Molecular Sciences retina cone photoreceptors retinitis pigmentosa rod-cone dystrophy gene therapy |
author_facet |
Mark M. Hassall Michelle E. McClements Alun R. Barnard Maria í. Patricio Sher A. Aslam Robert E. Maclaren |
author_sort |
Mark M. Hassall |
title |
Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy |
title_short |
Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy |
title_full |
Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy |
title_fullStr |
Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy |
title_full_unstemmed |
Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy |
title_sort |
analysis of early cone dysfunction in an in vivo model of rod-cone dystrophy |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-08-01 |
description |
Retinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a secondary degeneration. Changes in the gene expression profile of cone photoreceptor cells are likely to occur prior to observable physiological changes. To this end, we sought to achieve greater understanding of the changes in cone photoreceptor cells early in the degeneration process of the <i>Rho<sup>−/−</sup></i>mouse model. To account for gene expression changes attributed to loss of cone photoreceptor cells, we normalized PCR in the remaining number of cones to a cone cell reporter (<i>OPN1-GFP</i>). Gene expression profiles of key components involved in the cone phototransduction cascade were correlated with tests of retinal cone function prior to cell loss. A significant downregulation of the photoreceptor transcription factor <i>Crx</i> was observed, which preceded a significant downregulation in cone opsin transcripts that coincided with declining cone function. Our data add to the growing understanding of molecular changes that occur prior to cone dysfunction in a model of rod-cone dystrophy. It is of interest that gene supplementation of <i>CRX</i> by adeno-associated viral vector delivery prior to cone cell loss did not prevent cone photoreceptor degeneration in this mouse model. |
topic |
retina cone photoreceptors retinitis pigmentosa rod-cone dystrophy gene therapy |
url |
https://www.mdpi.com/1422-0067/21/17/6055 |
work_keys_str_mv |
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