Glucocorticoid and progesterone mechanisms in photoreceptor survival.

Death of retinal photoreceptors is the basis of prevalent blinding diseases. Since steroids might have a therapeutic role in retinal degenerations, we compared the protective effects of dexamethasone and progesterone on photoreceptor death induced by mifepristone and light exposure. Therefore, we studied the effective protection doses for each steroid in the two models. In addition, we analyzed changes in the levels of pro- and antiapoptotic molecules, glucocorticoid receptors α and ß (GRα and GRß), and rhodopsin under conditions of successful protection and photoreceptor survival. Mifepristone and light exposure selectively damaged photoreceptors. In light exposed retinas, photoreceptors mainly disappeared in the dorsotemporal region, while mifepristone produced a uniform damage. Dexamethasone and progesterone, at the same dose of 4 mg/kg/day for 2 days, preserved over 88% photoreceptor nuclei in both models. Assessment of cell death regulators showed that, in control retinas, both steroids activated BCL-XL, a prosurvival molecule, and decreased BID, a proapoptotic regulator. After steroid treatment of damaged retinas, BCL-XL, BCL2 and BAX showed characteristic patterns depending on the use of dexamethasone or progesterone on mifepristone or light exposed retinas. By contrast, BID decreased with any injury-steroid combination. Changes in GRα or GRß levels did not correlate with survival but were consistent with a mechanism of ligand induced downregulation of receptor expression. GRß might be upregulated by progesterone. Both dexamethasone and progesterone increased retinal rhodopsin stores, suggesting a link between photoreceptor protection and transduction pathways. Results show that dexamethasone and progesterone induced comparable but not identical protection responses in each model.

Inhibition of molting by cadmium in the crab Chasmagnathus granulata (Decapoda Brachyura).

The effect of cadmium on molting of the estuarine crab Chasmagnathus granulata was assayed. Adult males were eyestalk-ablated, in order to synchronically induce molting, and were then chronically exposed to cadmium at 0.25 or 0.50 mg/l. At the highest concentration, a significant mortality was detected at the time of molting, in the few crabs that could reach the E stage. However, most of the crabs exposed from the beginning of the premolt period (D(0) stage) to 0.50 mg/l of cadmium were arrested at the D(1)" stage. This effect was not seen when crabs were exposed to the same cadmium concentration from either D(1)"' or D(3) premolt stages. Crabs arrested by cadmium did not present any difference in the calcium content of carapace, compared to controls, while ecdysteroid levels of those crabs were similar to the ones of control crabs that were in the same premolt stage but could finally molt. These results suggest that cadmium could be preventing the normal peaking of ecdysteroids needed for molting. Since eyestalk-ablated crabs were used, a presumably direct effect of cadmium on Y-organ seems likely, by affecting cytoplasmatic calcium concentration and/or other actions.