Abstract
Purpose: :
It is not clear whether a mammalian retina contains a proliferative region similar to the ciliary margin zone (CMZ) of an aquatic vertebrate. Our study showed that cells continue to proliferate at the retinal-ciliary margin in challenged mouse retinas indicating a potential that cell cycle can be reactivated in the region. Therefore, we hypothesize that the mammalian retinal-ciliary margin retains proliferative potency and proliferation can be triggered by retinal shortages. Based on the paradigm that a specific retinal cell type inhibits the formation of the same type, we followed the response of the retinal-ciliary margin of mouse retnas with different degrees of retinal ganglion cell (RGC) loss at different developmental and adult stages.
Methods: :
To test the hypothesis, we traced the response of retinal-ciliary margin in a series of retinas with a spectrum of RGC loss. Cell proliferation, marked by BrdU and phosphohistone-3, as well as the activity of math5, a gene essential for RGC production, were examined at given different points.
Results: :
The math5 activity was prolonged to different degrees in the retinal-ciliary margin corresponding to the severity of RGC loss. Briefly, the less there are the RGCs, the longer the math5 is active in the retinal-ciliary margin. Also, we found that most cells in the ciliary margin are proliferative up to one month old, the latest time point we have examined.
Conclusions: :
Cells in the mouse retinal-ciliary margin retains the proliferative potential. Such a potential can be activated by lifting inhibition suggesting RGCs generate a negative feedback circuit for the production of new neurons.
Keywords: retina • ganglion cells • proliferation