RhoA and Its Role in Synaptic Structural Plasticity of Isolated Salamander Photoreceptors

Abstract

Thus, RhoA-ROCK activity reduces and retracts neuritic growth, but inhibition of activity increases neuritic development and blocks retraction. The results suggest that RhoA activation contributes to axon retraction by rod cells after retinal detachment, whereas inhibition of RhoA contributes to the neuritic sprouting seen in reattached and degenerating retina.

LIM Kinase, a Newly Identified Regulator of Presynaptic Remodeling by Rod Photoreceptors After Injury

“…To be consistent with previous studies, 15,16 we chose cells without an outer segment but with an axon terminal. Although rod opsin labeling predominantly localizes in the outer segments of rod photoreceptors in the intact retina, studies have shown that after retinal detachment and dissociation, rod opsin redistributes and is present throughout the entire plasma membrane of rod cells.…”

“…[9][10][11][12][13][14] To prevent potential visual loss after detachment due to disrupted circuitry, it is necessary to understand the mechanisms behind the reactive structural changes by photoreceptors. RhoA-Rho kinase (ROCK) activity 15,16 and Ca 2þ influx 17,18 have been reported to play a role in regulating axonal retraction by rod photoreceptors in both isolated tiger salamander rod cells and detached porcine retinas. This study expands these findings by examining (1) the role of ROCK's downstream effector, LIM kinase (LIMK) [19][20][21] ; (2) the role of p21-activated kinase (Pak), like ROCK, an upstream regulator of LIMK [21][22][23][24] ; and (3) the relationship between Ca 2þ influx and ROCK or LIMK in rod cell injury.…”

ROCK inhibitors in ocular disease

“…In salamander retinal cultures, rods retract their axons by 24 hours. However, rods maintained their morphology and showed no axonal retraction with 100 µM Y27632 pretreatment [97] and in similar conditions with even lower concentrations (10, 30, 100 µM) in a dose-dependent manner [98]. An in vitro retinal detachment model in porcine eyes demonstrated that RhoA activity increased immediately after detachment [94,99]; recent experiments, therefore, have explored short time periods after the detachment injury.…”

“…Moreover, at every time point, (on day 3, 7, 14, 21) but especially after one week, the optic nerve trauma related changes, such as retinal ganglion cell nuclei degeneration and cell loss and thinning of the retina, were less severe in the fasudiltreated group [91]. In salamander retinal cultures 100 µM Y27632 had different effects on photoreceptors depending on cell type [92]. For rods, it inhibited axonal retraction and slightly enhanced the rod process outgrowth; but for cones, it significantly increased the number of new process and the development of presynaptic varicosities.…”

“…RhoA was shown to be present in the inner and the outer retina of salamanders [97], and pigs [94]. From both in vitro and in vivo experiments, the RhoA-ROCK pathway was shown to take part in structural remodeling of photoreceptors, including rod axon retraction and cone neuritic outgrowth.…”