Abstract
Purpose :
In normal retinal development, the retinal waves stop at around the time of eye opening. However, the rd1 mice which have rapid onset of photoreceptor degeneration and are effectively blind by 3 weeks of age show rhythmic activity in RGCs and this hyperactivity is sustained well into adulthood. If the increased spontaneous activity is important in driving axon growth of RGCs in the developing retina, then these rd1 mice may extend their axon growth capacity long after the cessation of retinal waves. The present study was aimed to examine the effect of rhythmic activity on neurite outgrowth of developing retinal explants in rd1 mice.
Methods :
Retinal explants from P11, P15, and P22 mice were cultured with BDNF on the membrane inserts for 5 days to study the capacity of RGC neurite outgrowth. To quantify the extent of neurite outgrowth which was labeled by beta III tubulin (TUJ1) staining, images of the retinal explants from the confocal microscope were analyzed. The extent of neurite outgrowth was then characterized by dividing the total neurite area by the circumference of the explant.
Results :
While the extent of neurite outgrowth from retinal explants of P11 rd1 mice was not significantly different from that of the control, the axon growth capacity of RGCs was significantly enhanced in P15 and P22 rd1 mice when compared with the wildtype control, though the neurite outgrowth in P22 rd1 mice was still much less than that in P15 rd1 mice.
Conclusions :
The rhythmic activity of RGCs observed in rd1 mice is advantageous in promoting neurite outgrowth of retinal explants. Thus, enhancing the endogenously occurred neural activity may extend the axon growth capacity of RGCs into adulthood. This finding could lead to a therapeutic strategy that is able to prevent the gradual loss of the axon growth ability of RGCs in more mature retinas.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.