Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

containing solution (to competitively block Ca2+ influx) caffeine had no effect when added after complete inhibition, but when added during partial inhibition of responses, the Mg2+-induced inhibition was transiently reversed or halted. This suggests that Ca2+ influx was a prerequisite for the action of caffeine. 4. Ryanodine (1 uM) increased the responses of Merkel cell receptors to mechanical stimulation by 7-60% (mean+ S.E.M., 32 + 10 9%, n = 5, P < 0 05) but had no effect on St II receptor responses.5. The Ca2+-induced Ca2+ release (CICR) inhibitor procaine inhibited St I receptor responses in a concentration-dependent manner. Near-maximal inhibition was attained with 100,uM procaine. In four St I units, mean responses were depressed to 25 % of control values. When both procaine (100 uM) and caffeine (10 mM) were introduced together, no net effect was seen. The responses of St II receptors were little affected by up to 100 /SM procaine superfusion. 6. It is concluded that the mechano-electrical transduction process in St I receptors (but not St II) includes a CICR pathway. Taken with previous findings on the role of Merkel cells, it is likely that CICR is occurring in the Merkel cells.

Methamphetamine (METH) is a monoaminergic toxin that destroys dopamine terminals and causes astrogliosis in vivo. Oxidative stress has been shown to play an important role in the toxic effects of METH. In the present study, we sought to determine whether astrocytes are involved in METH-induced oxidative stress. Reactive oxygen species (ROS), ATP, and change in mitochondria membrane potential (delta psi(m)) were examined in cultured striatal, mesencephalic, and cortical astrocytes after 4 to 48 h of 4 mM METH treatment. Results showed that only striatal and mesencephalic astrocytes showed a significant increase in ROS formation from 8 and 12 h, respectively. At 48 h treatment, there was a 55 and 53% increase in ROS content in striatal and mesencephalic astrocytes, respectively, whereas cortical astrocytes showed only a 25% (not significant) increase. JC-1, a delta psi(m)-sensitive dye, showed a decrease in delta psi(m) at 8 h treatment for striatal and mesencephalic astrocytes and at 12 h for cortical astrocytes. Astrocytes from all three regions showed a similar pattern of initial increase followed by a decrease in ATP content, with striatal astrocytes resulting in a maximum depletion (39% of control value) at 48 h treatment. These findings showed that METH treatment resulted in the formation of ROS in the order of striatal > mesencephalic > cortical astrocytes. Although the formation of ROS did not severely interfere with ATP production, a depolarization of mitochondria was observed. The present study suggested that astrocytes may be an important element governing the selective vulnerability to the striatum to METH-induced oxidative stress.

No abstract