Effect of the calcium antagonist, nifedipine, on ischemic retinal dysfunction.
The therapeutic effectiveness of calcium channel antagonists (CCA) in hypertension and angina are well established. More recently, CCAs have also been demonstrated to ameliorate neurologic dysfunction that often accompanies ischemia associated with subarachnoid hemorrhage and stroke. We have hypothesized that retinal degeneration associated with ischemia may also result from the accumulation of calcium intracellularly, so-called "Ca++ overload". To test this hypothesis, a rat model of acute retinal ischemia, produced by direct occlusion of posterior ciliary and central retinal arteries, was developed. The extent of retinal dysfunction induced by ischemia was evaluated by electroretinograms (ERGs). Occlusion of the retinal arteries resulted in the disappearance of both a- and b-waves during the occlusion period (30 minutes) in vehicle-treated rats. Total retinal ischemia did not produce any significant change in magnitude of ERG a-wave amplitude during three-hours of reperfusion. However, ERG b-waves amplitudes were significantly reduced by more than 60%. In rats, pretreatment with nifedipine (0.33 to 3.3 mg/kg, i.p.) 30 minutes prior to the occlusion of the retinal vessels produced a significant dose-dependent increase in the recovery of b-wave amplitude when compared to vehicle-treated rats. These data support the idea that "Ca++ overload", resulting from the deregulation of intracellular Ca++ homeostasis, is a primary factor involved in ischemic retinal degeneration and that CCAs can protect the retina from ischemic damage.
Crosson
C E
CE
Houston Biotechnology, Incorporated, The Woodlands, Texas.
Willis
J A
JA
Potter
D E
DE
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D015356:Retinal Artery Occlusion / Q000150:complications; D012164:Retinal Diseases / Q000209:etiology / Q000503:physiopathology*
D009543:Nifedipine