Analysis of Cell Surface Markers Specific for Transplantable Rod Photoreceptors

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2013 Oct 23

PMID 24146539

Citations 11

Authors

Kai Postel

Jessica Bellmann

Victoria Splith

Marius Ader

Affiliations

Soon will be listed here.

Abstract

Purpose: Transplantation of cells into retinas affected by degenerative diseases to replace dying photoreceptors represents a promising therapeutic approach. Young photoreceptors of 4-day-old mice show the highest capacity to integrate into the retinas of adult mice following grafting. Additional enrichment of these donor cells before transplantation with cell surface marker-dependent sorting methods further increases success rates. Currently, defined cell surface markers specific for transplantable photoreceptors that can be used for enrichment are limited. Therefore, identifying alternative targets would be advantageous.

Methods: Microarray data of young rod photoreceptors were analyzed using the Database for Annotation, Visualization and Integrated Discovery combined with a literature search to identify genes encoding for proteins containing extracellular domains. Candidate genes were further analyzed with reverse transcriptase polymerase chain reaction (RT-PCR) for their retinal specificity. In situ hybridization and immunohistochemistry were used to identify their localization within the retina.

Results: Enrichment of candidates by Database for Annotation, Visualization and Integrated Discovery revealed 65 proteins containing extracellular domains. Reverse transcriptase polymerase chain reaction identified Atp8a2, Cacna2d4, Cadm2, Cnga1, Kcnv2, and Pcdh21 as expressed in the retina and only a few additional tissues. In situ hybridization and immunohistochemistry showed specificity of Cacna2d4, Kcnv2, and Pcdh21 for photoreceptors in the retinas of young mice.

Conclusions: Cacna2d4, Kcnv2, and Cnga1 were identified as specific for target cells in the retinas of young mice and could serve as candidates for rod photoreceptor enrichment to replace cells in retinal degenerative diseases.

Citing Articles

Generation of an RCVRN-eGFP Reporter hiPSC Line by CRISPR/Cas9 to Monitor Photoreceptor Cell Development and Facilitate the Cell Enrichment for Transplantation.

Guan Y, Wang Y, Zheng D, Xie B, Xu P, Gao G Front Cell Dev Biol. 2022; 10:870441.

PMID: 35573687 PMC: 9096726. DOI: 10.3389/fcell.2022.870441.

Integrative RNA-seq and ATAC-seq analyses of phosphodiesterase 6 mutation-induced retinitis pigmentosa.

Xu W, Li Y, Dong Y, Xiao L, Li L, Jiao K Int Ophthalmol. 2022; 42(8):2385-2395.

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Regenerative medicine in the retina: from stem cells to cell replacement therapy.

Oswald J, Baranov P Ther Adv Ophthalmol. 2018; 10:2515841418774433.

PMID: 29998222 PMC: 6016968. DOI: 10.1177/2515841418774433.

Rebuilding the Missing Part-A Review on Photoreceptor Transplantation.

Santos-Ferreira T, Borsch O, Ader M Front Syst Neurosci. 2017; 10:105.

PMID: 28105007 PMC: 5214672. DOI: 10.3389/fnsys.2016.00105.

Three-dimensional retinal organoids from mouse pluripotent stem cells mimic development with enhanced stratification and rod photoreceptor differentiation.

Chen H, Kaya K, Dong L, Swaroop A Mol Vis. 2016; 22:1077-1094.

PMID: 27667917 PMC: 5017542.

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