Senescence-associated β-galactosidase activity in the developing avian retina.

Abstract

Senescence-associated β-galactosidase (SA-β-GAL) histochemistry is the most commonly used biomarker of cellular senescence. These SA-β-GAL-positive cells are senescent embryonic cells that are usually removed by apoptosis from the embryo, followed by macrophage-mediated clearance. Some authors have proposed that SA-β-GAL activity in differentiated neurons from young and adult mammals cannot be uniquely attributed to cell senescence, whether in vivo or in vitro. Using the developing visual system of the chicken as a model, the present study found that SA-β-GAL detected in the developing retina corresponded to lysosomal β-galactosidase activity, and that SA-β-GAL activity did not correlate with the chronotopographical distribution of apoptotic cells. However, SA-β-GAL staining in the undifferentiated retina coincided with the appearance of early differentiating neurons. In the laminated retina, SA-β-GAL staining was concentrated in the ganglion, amacrine, and horizontal cell layers. The photoreceptors and pigment epithelial cells also exhibited SA-β-GAL activity throughout retinal development. We have also found that SA-β-GAL staining strongly correlated p21 immunoreactivity. In conclusion, the results clearly show that SA-β-GAL activity cannot be regarded as a specific marker of senescence during retinal development, and that it is mainly expressed in subpopulations of postmitotic neurons, which are nonproliferative cells, even at early stages of cell differentiation.