{Reference Type}: Journal Article
{Title}: Photoreceptor proliferation and dysregulation of cell cycle genes in early onset inherited retinal degenerations.
{Author}: Gardiner KL;Downs L;Berta-Antalics AI;Santana E;Aguirre GD;Genini S;
{Journal}: BMC Genomics
{Volume}: 17
{Issue}: 0
{Year}: Mar 2016 11
{Factor}: 4.547
{DOI}: 10.1186/s12864-016-2477-9
{Abstract}: <B>BACKGROUND: </B>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).<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.