Critical period for vision-dependent modulation of postnatal retinal neurogenesis

Abstract

It is generally accepted that retinal neurogenesis in mammals ceases shortly after birth and that stem/progenitor cells found in the postnatal eyes of mice and humans are in the quiescent state. In the present study, we have investigated postnatal retinal neurogenesis and its modulation by visual experience in the mouse model. Four age groups (P26, P45, P72, and P94) of transgenic mice expressing green fluorescent protein (GFP) in the retinal progenitor cells under the control of nestin regulatory elements were examined for the presence of nestin-GFP-positive proliferating progenitor cells in the retina. Contrary to the previously held belief, we found a significant number of proliferating progenitors at the retinal periphery in all age groups examined. The majority of these cells gave rise to photoreceptors as revealed by the genetic cell fate mapping experiments. The intensity of neurogenesis was declining with age, and strongly correlated with eye growth. Visual form deprivation resulted in a significant increase in the intensity of peripheral neurogenesis, which correlated strongly with the induced ocular growth. The susceptibility to both form-deprivation-induced increase in the peripheral neurogenesis and form-deprivation-induced increase in the ocular growth declined with age ceasing completely around P70, which marked the end of the critical period for the vision-dependent modulation of both ocular growth and postnatal retinal neurogenesis. Thus, neurogenesis in the peripheral retina of young mice is modulated by visual input, but only during a critical period in postnatal development.