Abstract
Purpose: :
Estrogens are well–known to be vasodilators and to increase blood flow. We have recently showed that post–menopausal women on hormone replacement therapy presented better retinal arterial blood flow as measured with the Canon Laser Blood Flowmeter (MC Deschênes et al., 2005). Since rats, like humans, have estrogen receptors in the retina (Wickham LA et al., 1998, 2000; Kobayashi K et al., 1998), we investigated whether estradiol treatment increases whole–mount retinal blood flow in an ovariectomized rat model.
Methods: :
Bilateral ovariectomy was performed in 12 Brown Norway rats and silastic capsules were implanted in the nape of the neck for timed release of either 100% cholesterol (OVx control group, n=5) or 25% estradiol + 75% cholesterol (OVx+E2–treated group, n=7). Six weeks later, the blood flow tracer N–Isopropyl–p–iodoamphetamine ([14C]–IMP, ARC, St. Louis, USA, 100uCi/Kg) was injected through the femoral vein over a 30–second period in the awake rats. Cardiovascular, blood gas, chemistry and hematological parameters were monitored prior to the injection. At the end of the injection, the rats were sacrificed, eyes harvested and post–fixed in 4% paraformaldehyde overnight. The following day, the retinas were whole–mounted on a slide and applied on a Kodak film for 10 days. Using the MCID Basic Software (v7.0, Imaging Research, Mississauga, ON, Canada) the autoradiograms were read with a circular sampling region of 0.8mm2 at 1,2,3,4 mm isopters away from the center of the optic nerve head for each retinal quadrant. Retinal blood flow was determined from the local retinal uptake index (LRUI) calculated according to Temma T et al., (2004).
Results: :
The OVx+E2 group of rats had significantly elevated serum E2 compared to the OVx group of rats (100.9+/–15.6 vs 19.4+/–2.1 pg/ml, p=<0.01, t–test). Morever, the LRUIs of the [14C]–IMP in the whole–mount retinas were significantly greater in the OVx+E2 group of rats at the 2 ( 9.7+/–1.9 vs 6.9+/–1.8, p=.03), 3 (7.5+/–1.5 vs 5.2+/–1.5, p=.03) , and 4 (4.6+/–0.7 vs 3.5+/–0.8, p=.04) mm isopters compared to the OVx control group of rats using a t–test.
Conclusions: :
Estradiol induced significant increases in the LRUI of [14C]–IMP, an indicator of blood flow, in whole–mount retina in a rat model of ovariectomy. This increase ranges from 32 to 45% for the 2, 3 and 4 mm isopters. These findings indicate a beneficial effect of estrogens treatment on the retinal blood flow in this model.
Keywords: blood supply • retina • imaging/image analysis: non-clinical