SOME BIOCHEMICAL AND PATHOPHYSIOLOGICAL ASPECTS OF LONG-TERM ELEVATION OF BRAIN ORNITHINE CONCENTRATIONS

Mice and chicken were given 5-fluoromethylornithine (5FMOrn), a select ive inactivator of ornithine aminotransferase (OAT) over extended peri ods of time. This treatment allowed us to maintain elevated concentrat ions of ornithine in all tissues. Since gyrate atrophy, an autosomal r ecessive human disease, is characterized by the absence of OAT, specia l emphasis was put on the study of the visual system. Ophthalmoscopic and histologic examinations of the eye as well as electroretinograms a nd locomotor behaviour demonstrated an unimpaired visual system and br ain. No toxic effects were observable in the treated mice. Likewise, c hick embryo development was normal in spite of highly elevated brain a nd tissue ornithine concentrations. A likely explanation for the absen ce of toxic effects of 5FMOrn treatment, disregarding the non-toxicity of ornithine, is the fact that 10-20% of tissue OAT is refractory to inactivation by 5FMOrn. This residual activity may be sufficient to ma intain vital functions.