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

BMC Genomics

Research Article

Evelyn Santana¹  Louise Downs¹  Gustavo D. Aguirre¹  Kristin L. Gardiner¹  Sem Genini¹  Agnes I. Berta-Antalics² 

[1] Section of Ophthalmology, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, 19104, Philadelphia, PA, USA;Section of Ophthalmology, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, 19104, Philadelphia, PA, USA;Augenklinik Uniklinik Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany;

关键词: Canine models;    Cell cycle;    erd;    Hippo pathway;    Photoreceptor degeneration;    Photoreceptor mitosis;    rcd1;    xlpra2;   

DOI  :  10.1186/s12864-016-2477-9

 received in 2015-11-15, accepted in 2016-02-16,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMitotic 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).ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Gardiner et al. 2016