Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo.

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca2+ levels to RGC death from axon injury. We find that axonal Ca2+ elevations from optic nerve injury do not propagate over distance or reach RGC somas, and acute and chronic Ca2+ dynamics do not affect RGC survival. Instead, we discover that baseline Ca2+ levels vary widely between RGCs and predict their survival after axon injury, and that lowering these levels reduces RGC survival. Further, we find that well-surviving RGC types have higher baseline Ca2+ levels than poorly surviving types. Finally, we observe considerable variation in the baseline Ca2+ levels of different RGCs of the same type, which are predictive of within-type differences in survival.

Pre-swing deficits in forward propulsion, swing initiation and power generation by individual muscles during hemiparetic walking.

Clinical studies of hemiparetic walking have shown pre-swing abnormalities in the paretic leg suggesting that paretic muscle contributions to important biomechanical walking subtasks are different than those of non-disabled individuals. Three-dimensional forward dynamics simulations of two representative hemiparetic subjects with different levels of walking function classified by self-selected walking speed (i.e., limited community=0.4-0.8 m/s and community walkers = or > 0.8m/s) and a speed-matched control were generated to quantify individual muscle contributions to forward propulsion, swing initiation and power generation during the pre-swing phase (i.e., double support phase proceeding toe-off). Simulation analyses identified decreased paretic soleus and gastrocnemius contributions to forward propulsion and power generation as the primary impairment in the limited community walker compared to the control subject. The non-paretic leg did not compensate for decreased forward propulsion by paretic muscles during pre-swing in the limited community walker. Paretic muscles had the net effect to absorb energy from the paretic leg during pre-swing in the community walker suggesting that deficits in swing initiation are a primary impairment. Specifically, the paretic gastrocnemius and hip flexors (i.e., iliacus, psoas and sartorius) contributed less to swing initiation and the paretic soleus and gluteus medius absorbed more power from the paretic leg in the community walker compared to the control subject. Rehabilitation strategies aimed at diminishing these deficits have much potential to improve walking function in these hemiparetic subjects and those with similar deficits.