RESUMEN
Ocular melanin is found in the uveal tract and in the pigmented epithelial layer of the retina. Many structurally and pharmacologically unrelated drugs from different therapeutic classes bind to melanin. Examples include numerous drugs acting on the central nervous system, beta-blockers, beta-agonists, antimalarial drugs, sympathomimetic amines, and antibiotics. The critical factors are the acid/base status and the lipophilicity of the molecule. In all cases, there are no direct consequences of drug-melanin binding. Drug-related toxic effects on the retina described in humans and animals are unrelated to melanin binding: melanin binding and retinal toxicity are two separate entities, the latter being related to the intrinsic toxicity of the compound rather than its ability to bind. Chloroquine and phenothiazines are often used as examples of drugs with retinal toxicity linked to melanin binding. In both cases however, experimental data show that the toxic mechanism is unrelated to binding. Melanin binding has also been found to be protective against the ocular toxicity of some drugs. In conclusion, we believe that potential ocular toxicity of future drugs can be assessed adequately by conducting well-designed toxicology studies, and using nonpigmented rodents in addition to pigmented nonrodent species remains fully justified. Binding of drugs to eye melanin is not predictive of ocular toxicity.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Melaninas/efectos adversos , Melaninas/metabolismo , Preparaciones Farmacéuticas/metabolismo , Epitelio Pigmentado Ocular/metabolismo , Úvea/metabolismo , Animales , Cloroquina/toxicidad , Ojo/efectos de los fármacos , Humanos , Fenotiazinas/toxicidad , Unión ProteicaRESUMEN
Examination of the eye in experiments designed to test the toxicity of drugs or chemicals is of considerable importance and the investigator must have a clear idea of the spontaneous eye changes he can expect in the test species. We have attempted to review the literature relating to commonly used laboratory animals--the rat, mouse, and dog as well as the hamster--but as there is still only a handful of workers that publish their findings, the literature is not fully comprehensive. Our own unpublished data have been used to try and provide a more complete account. There is, therefore, a considerable need for further work in this area and, in the future, newer techniques such as electron microscopy and histochemistry can help us in the understanding of the pathogenesis of age-related changes in laboratory animals.