Otx2 And VegfA Expression And P53-Otx1 Differentiation Pathway In Proliferative Vitreoretinopathy

Abstract

 

Purpose:

 

Otx1 and Otx2 are a family of homeobox genes involved in the eye and central nervous system development, driving embryonic stem cells differentiation. Otx2 regulates rods, cones and bipolar cells differentiation, and Otx1 is a marker of the ciliary body and the anterior pars of the retina. Recently it has been demonstrated that p53 protein directly regulates Otx1 gene expression during breast cancer stem cells differentiation, and that this differentiation pathway is present in the adult retina. The aim of the study was evaluate the pathway involved in proliferative retinopathy (PVR) disease, analyzing expression levels of Otx1, Otx2, Tp53 and VegfA genes.

 

Methods:

 

Adult human retina was taken during vitreoretinal surgery in two patients affected by PVR in middle periphery retina. RNA from retinal tissues was extracted and retro-transcribed, and a qRT-PCR assay was performed to evaluate expression levels of Otx1, Otx2, Tp53 and VegfA genes. Normal human retinal tissue from autopsy was used as control.

 

Results:

 

We showed increase of Otx2 and VegfA gene expression levels and down-regulation of p53-Otx1 pathway in retina from PVR patients (Figure 1, values for control, patient 1 and 2)

 

Conclusions:

 

Retinal detachment induces activation of pigment epithelial and glial cells, that display de-differentiated cells characteristics, reminiscent of the non-differentiated glial cells in ontogenesis. The stemness re-acquisition in the PVR patients retina is confirmed by down-regulation of p53-Otx1 differentiation pathway, and by increase of Otx2 gene expression levels, that similarly activates a period of post-natal plasticity into the visual cortex. Finally we showed VegfA over-expression, testing the proliferative status of the vascular-endothelial cells in this disease.  

 

Keywords: gene/expression • retinal degenerations: cell biology • vascular endothelial growth factor