SPACR Encoded by IMPG1 Is Essential for Photoreceptor Survival by Interplaying between the Interphotoreceptor Matrix and the Retinal Pigment Epithelium.

Autor:	Olivier G; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Brabet P; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Pirot N; RHEM, IRCM-INSERM, 34000 Montpellier, France., Broyon M; RHEM, IRCM-INSERM, 34000 Montpellier, France., Guillou L; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Cazevieille C; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Sar C; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Quiles M; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Sarzi E; INSERM, University Claude Bernard, 69100 Lyon, France., Pequignot M; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Andreo E; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Roubertie A; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France.; INM, University of Montpellier, INSERM, CHU Montpellier, 34000 Montpellier, France., Meunier I; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France.; INM, University of Montpellier, INSERM, CHU Montpellier, 34000 Montpellier, France., Muller A; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Kalatzis V; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France., Manes G; Institute for Neurosciences of Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, 34091 Montpellier, France.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2022 Aug 23; Vol. 13 (9). Date of Electronic Publication: 2022 Aug 23.
DOI:	10.3390/genes13091508
Abstrakt:	Several pathogenic variants have been reported in the IMPG1 gene associated with the inherited retinal disorders vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP). IMPG1 and its paralog IMPG2 encode for two proteoglycans, SPACR and SPACRCAN, respectively, which are the main components of the interphotoreceptor matrix (IPM), the extracellular matrix surrounding the photoreceptor cells. To determine the role of SPACR in the pathological mechanisms leading to RP and VMD, we generated a knockout mouse model lacking Impg1 , the mouse ortholog. Impg1 -deficient mice show abnormal accumulation of autofluorescent deposits visible by fundus imaging and spectral-domain optical coherence tomography (SD-OCT) and attenuated electroretinogram responses from 9 months of age. Furthermore, SD-OCT of Impg1 -/- mice shows a degeneration of the photoreceptor layer, and transmission electron microscopy shows a disruption of the IPM and the retinal pigment epithelial cells. The decrease in the concentration of the chromophore 11- cis -retinal supports this loss of photoreceptors. In conclusion, our results demonstrate the essential role of SPACR in maintaining photoreceptors. Impg1 -/- mice provide a novel model for mechanistic investigations and the development of therapies for VMD and RP caused by IMPG1 pathogenic variants. Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Databáze:	MEDLINE
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