Elevated plasma aldosterone levels are associated with a reduction in retinal ganglion cell survival

Abstract

Objective: The purpose of this article is to investigate the relationship between the plasma concentration of aldosterone and changes in the number of retinal ganglion cells (RGCs) after systemic administration of aldosterone.

Methods: An osmotic minipump that was subcutaneously implanted into the midscapular region of rats administered 40, 80 or 160 μg/kg/day aldosterone or vehicle. Enzyme immunoassay kits were used to measure the plasma aldosterone concentrations two weeks after the systemic administration of aldosterone or vehicle. Six weeks after these systemic administrations, the number of RGCs was measured.

Results: The plasma aldosterone concentrations at two weeks after systemic administration of vehicle or 160 μg/kg/day aldosterone were 238 ± 17 pg/ml and 1750 ± 151 pg/ml (748.5% ± 183.2%), respectively. There was a significant decrease in the number of RGCs in the central retina of the rats after the administration of either 80 or 160 μg/kg/day aldosterone. In the peripheral retina, however, there was a significant decrease in the number of RGCs in 40, 80 or 160 μg/kg/day aldosterone. There was a significant correlation between the number of RGCs and plasma aldosterone concentration.

Conclusions: After systemic administration of aldosterone, there was a negative correlation between the plasma aldosterone concentration and the number of RGCs.

Keywords: Aldosterone; glaucoma; plasma aldosterone concentration; rat; retinal ganglion cell.

Figure 1.

Plasma aldosterone concentration after being treated with vehicle or 40, 80 or 160 μg/kg/day aldosterone. Results are expressed as the mean ± SEM (n = 6: vehicle, n = 6: 40 μg/kg/day aldosterone, n = 6: 80 μg/kg/day, n = 6: 160 μg/kg/day). *p < 0.001 vs control (Dunnett’s multiple comparison test).

Figure 2.

Effect of aldosterone on retinal ganglion cell (RGC) death. (a) Retrograde labeling of RGCs treated with vehicle or 40, 80 and 160 μg/kg/day aldosterone for six weeks. Micrographs of the central and peripheral areas were taken approximately 1 and 4 mm away from the optic nerve head. Scale bar, 100 μm. RGCs were counted in the central (b) and peripheral (c) areas. Results are expressed as the mean ± SEM (n = 6: vehicle, n = 6: 40 μg/kg/day aldosterone, n = 6: 80 μg/kg/day, n = 6: 160 μg/kg/day). *p < 0.001 vs control (Dunnett’s multiple comparison test).

Figure 3.

Scatter plots showing association between plasma aldosterone concentration and the number of retinal ganglion cells (RGCs) in the central retina (a) and peripheral retina (b). (a) Correlation coefficient = −0.911. Regression equation y = −1.33x + 2807. (b) Correlation coefficient = −0.869. Regression equation y = −0.96x + 2512.

Figure 4.

Aldosterone-induced apoptosis one week after systemic administration of aldosterone. The TUNEL-positive cells are indicated by arrows. Scale bar. TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling.