Ornithine decarboxylase activity in rabbit retina following treatment with alpha-difluoromethylornithine.
The rabbit retina has been utilized as a model for the study of abnormal cellular proliferation on the retinal surface and into the vitreous, a process commonly initiated by trauma and generally leading to retinal detachment. This study characterizes the ability of alpha-difluoromethylornithine (alpha-DFMO), a suicide inactivator of L-ornithine decarboxylase (EC 4.1.1.17) to inactivate normal retinal ornithine decarboxylase (ODC) activity in the crude supernatant fraction after incubation with different concentrations of alpha-DFMO and at various times after intraocular administration. Partial inactivation of ODC activity occurred following preincubation of crude retinal supernatant fraction with 10(-5) M alpha-DFMO (N = 3; 34 +/- 6.9% of control), whereas preincubation with 10(-8) M alpha-DFMO did not alter ODC activity significantly (N = 3; 94 +/- 2% of control). Different concentrations of alpha-DFMO administered intraocularly inactivated retinal ODC activity to varying degrees with different rates of recovery. No gross toxicity occurred with ocular tissues following intravitreal administration of alpha-DFMO as determined by electrophysiologic measurements, by indirect examination of the retina, and by measurement of intraocular pressure. These results suggest that alpha-DFMO may be a useful tool in which to define the physiologic role of ODC and polyamines in intraocular cellular proliferative diseases.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D065108:Ornithine Decarboxylase Inhibitors; D011817:Rabbits; D012160:Retina / Q000201:enzymology*; D013997:Time Factors
D065108:Ornithine Decarboxylase Inhibitors; D000518:Eflornithine