RESUMEN
PURPOSE: To investigate, using full-field ERG, the retinal function in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN(3) gene. METHODS: Batten disease status of five patients was confirmed by the presence of vacuolated lymphocytes in peripheral blood and the identification of mutations in the Batten disease gene (CLN(3)). Visual acuity, fundus appearance, and full-field ERG were examined in all patients (age 4-19 years). The examination was repeated in one patient after 16 months. RESULTS: Three unrelated patients were homozygous for the most common mutation in CLN(3), the 1.02 kb deletion; two patients (sisters) were heterozygous for the 1.02 kb deletion and an as yet unidentified mutation in the CLN(3) gene. Full-field ERG recordings in all five patients demonstrated no rod responses and only small remaining cone responses, which could be detected with 30 Hz-flicker stimulation. Re-examination of a six-year-old girl after 16 months revealed a fast progression of the retinal degeneration. CONCLUSION: Full-field ERG recordings in Batten disease patients, both homozygous and heterozygous for the 1.02 kb deletion in the CLN( 3) gene, confirm retinal degeneration to be severe, widespread, and with a rapid progression early in the disease course. The onset of visual failure may be delayed when compared to the classic disease course, particularly in patients who are not homozygous for the most common CLN(3) mutation, a 1.02 kb deletion. In that case, the disease progression in terms of other symptoms may also be further delayed.
Asunto(s)
Glicoproteínas de Membrana , Chaperonas Moleculares , Mutación , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/fisiopatología , Proteínas/genética , Retina/fisiopatología , Degeneración Retiniana/fisiopatología , Adolescente , Adulto , Niño , Preescolar , ADN/análisis , ADN/sangre , Análisis Mutacional de ADN , Progresión de la Enfermedad , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Degeneración Retiniana/genética , Agudeza VisualRESUMEN
The adenine nucleotide pool of rabbit retina was labeled by an intravitreal injection in vivo of [3H]adenosine. Practically all the radioactivity was retained in the form of adenine nucleotides. The relative proportion of [3H]adenine nucleotides was the same as that of endogenous nucleotides. Potassium depolarization (43.6 mM) in vitro caused a rapid increase in the rate of release of radioactive purines. The radioactive material was composed of hypoxanthine, xanthine, inosine and trace amounts of adenine, adenosine and adenine nucleotides. The release of radioactive purines was delayed and reduced by the addition of the nucleoside inhibitor dipyridamole suggesting that the purines may be released in the form of nucleosides. Similarly, the addition of the ecto 5'-nucleotidase inhibitor alpha, beta-methylene ADP (AOPCP) did not alter the release of radioactivity or the composition of the released purines. Endogenous hypoxanthine, xanthine and inosine could be detected in the effluents, but there was only a very modest increase following potassium depolarization. There was a slight, but significant, decrease in the release of endogenous adenosine and increase in AMP after AOPCP. It is concluded that there is an intensive uptake and phosphorylation of adenosine in the rabbit retina. Depolarization induces release of radioactive purine nucleosides and bases. Most of these compounds appear to be released as such, but in addition there may be a small (maximally a few per cent of the total) fraction of the purines that are released as nucleotides.
Asunto(s)
Nucleótidos de Adenina/metabolismo , Purinas/metabolismo , Retina/metabolismo , Adenina/metabolismo , Adenosina/metabolismo , Adenosina Difosfato/análogos & derivados , Adenosina Difosfato/farmacología , Animales , Dipiridamol/farmacología , Potenciales Evocados , Femenino , Hipoxantina , Hipoxantinas/metabolismo , Técnicas In Vitro , Masculino , Potasio/farmacología , Conejos , Retina/efectos de los fármacos , TritioRESUMEN
The experimental biologist faces two kinds of ethical problems: practical and philosophical. The practical problems comprise increased costs of experimental animals, and the risk of being harassed or even raided by animal activists. There is also today a growing bureaucratic ethics overhead that has to be paid for, one way or another. The philosophical problems are the true ethical problems. Most laws and regulations emphasize that pain and agony should be minimized, but it is shown that this is neither always necessary nor always adequate. Scientists expect logical reasoning and opinions based on facts, but it is easy to find examples that the public opinion is quite illogical concerning pain and agony. For instance, you may under certain circumstances very well torture and kill animals just for pleasure. Our present legislation should be amended so as to concur better with current public views on how animals should be treated. The Swedish Committees on Animal Experimentation Ethics were intended to help scientists understand the demands of the public opinion. It is doubtful if they have been successful. The ethics of animal experimentation are perforce centered on the experimenter. He alone, at the final moment, makes the decision whether or not to use and, eventually, to kill the animal. When he kills, he obviously has a reason for doing so, and has decided that the purpose justifies the action. With the very large increase in the number of animal experiments in the last few decades, society has justifiably become increasingly concerned about the ethical considerations involved.(ABSTRACT TRUNCATED AT 250 WORDS)