Photoreceptor proliferation and dysregulation of cell cycle genes in early onset inherited retinal degenerations

4Citations
Citations of this article
31Readers
Mendeley users who have this article in their library.

This artice is free to access.

Abstract

Background: Mitotic terminally differentiated photoreceptors (PRs) are observed in early retinal degeneration (erd), an inherited canine retinal disease driven by mutations in the NDR kinase STK38L (NDR2). Results: We demonstrate that a similar proliferative response, but of lower magnitude, occurs in two other early onset disease models, X-linked progressive retinal atrophy 2 (xlpra2) and rod cone dysplasia 1 (rcd1). Proliferating cells are rod PRs, and not microglia or Müller cells. Expression of the cell cycle related genes RB1 and E2F1 as well as CDK2,4,6 was up-regulated, but changes were mutation-specific. Changes in cyclin expression differed across all genes, diseases and time points analyzed, although CCNA1 and CCNE1 expression increased with age in the three models suggesting that there is a dysregulation of cell cycle gene expression in all three diseases. Unique to erd, however, are mutation-specific changes in the expression of NDR kinases and Hippo signaling members with increased expression of MOB1 and LATS1 in the newly generated hybrid rod/S-cones. Conclusions: Our data raise the intriguing possibility that terminally differentiated normal PRs are kept from dividing by NDR2-MOB1 interaction. Furthermore, they provide the framework for the selection of candidate genes for further investigation as potential targets of therapy.

Cite

CITATION STYLE

APA

Gardiner, K. L., Downs, L., Berta-Antalics, A. I., Santana, E., Aguirre, G. D., & Genini, S. (2016). Photoreceptor proliferation and dysregulation of cell cycle genes in early onset inherited retinal degenerations. BMC Genomics, 17(1). https://doi.org/10.1186/s12864-016-2477-9

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free