Estrogen Protects Retinal Ganglion Cell from Death in Chronically Elevated Intraocular Pressure in Ovariectomized Rats

Abstract

Purpose: : To investigate whether estrogen can protect retinal ganglion cell (RGC) from death in a chronic glaucoma model in ovariectomized rats.

Methods: : Unilaterally chronic elevation of intraocular pressure (IOP) was induced in 30 ovariectomized adult Sprague–Dawley rats by repeated laser trabecular meshwork photocoagulation using a krypton laser with wavelength of 532 nm. Two weeks later, after a moderate elevation of IOP was reached in laser treated eye, 17ß–estradiol (50µg/kg) or physiological saline (vehicle) was subcutaneously injected randomly, on every other day for 5 weeks. The eyes were then enucleated and the retinal section was stained with H&E. The density of RGC was quantitatively analyzed. RGC apoptosis was assayed by TdT–mediated biotin–dUTP nick end labeling (TUNEL), and the expression level of bcl–2, caspase 3 and bax was determined by real–time fluorescent quantitative reverse transcription polymerase chain reaction (RT–PCR).

Results: : After the elevated IOP (mean 24.66±3.82 mmHg) was maintained for 7 weeks, the number of surviving RGC in 17 ß–estradiol treated eyes and in vehicle treated eyes was 5.83±1.47 and 3.67±0.82 per 100 um of length in retinal sections as linear cell densities, respectively (p<0.000). The number of TUNEL–positive cells in the ganglion cell layer of 17 ß–estradiol treated eyes and vehicle treated eyes was 2.83±0.98 and 4.33±1.03 per 50 um of width of the retinal area at 2 mm periphery from the center of the optical nerve head, respectively (p=0.028). The expression of bcl–2 mRNA was increased (p=0.022) and that of caspase 3 mRNA was decreased (p=0.040) in 17 ß–estradiol treated eyes. There was no significant difference in expression of bax between these two groups.

Conclusions: : Estrogen improved survival of RGCs from chronic experimentally elevated IOP in ovariectomized rats, suggesting that estrogen has a neuroprotective effect on RGCs in the glaucomatous eyes.

Keywords: neuroprotection • ganglion cells • intraocular pressure