Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome

Abstract

Background: Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different. Patients and Methods: In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay. Results: The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (± SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (± 1.74), range: (2.37–6.76), whereas in patients without Flammer syndrome they were 1.10 (± 0.08), range: 1.00–1.20. Our own normal values are: 1.56 (± 0.30), range: (0.90–2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell. Conclusion: Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow reduction is due to retinal degeneration and how much to the Flammer syndrome? We hypothesise that Flammer syndrome leads to an additional increase of the endothelin-1 level and an additional decrease of ocular blood flow in retinitis pigmentosa patients. Further studies are needed to analyse the causal relationship between retinitis pigmentosa and Flammer syndrome and evaluate potential therapeutic implications.

Zusammenfassung

Hintergrund: Endothelin-1 ist ein vasokonstriktives Peptid, das entscheidend die Augendurchblutung beeinflusst. Patienten mit Retinitis pigmentosa haben oft sowohl Symptome und Zeichen eines Flammer-Syndroms, als auch eine reduzierte Augendurchblutung. Wir untersuchten daher die Endothelin-1-Plasmaspiegel bei Retinitis -pigmentosa-Patienten mit und ohne einem Flammer-Syndrom. Patienten und Methoden: Der Phänotyp der Retinitis-pigmentosa-Patienten wurde nach klinischen Befunden klassifiziert. Blutproben wurden entnommen von 6 Retinitis-pigmentosa-Patienten mit und 4 Retinitis-pigmentosa-Patienten ohne Flammer-Syndrom, sowie von 30 Kontrollpersonen vom gleichen Alter und Geschlecht. Die Endothelin-1-Plasmaspiegel wurden durch spezifische Radioimmunoassays bestimmt. Ergebnisse: Die Endothelin-1-Plasmaspiegel bei Retinitis pigmentosa mit einem Flammer-Syndrom waren signifikant höher als bei Retinitis pigmentosa ohne Flammer-Syndrom. Die Endothelin-1-Konzentrationen in pg/ml waren bei Retinitis-pigmentosa-Patienten mit Flammer-Syndrom zwischen 2,37–6,76, mit einem Mittelwert (± SD) von 4,95 (± 1,74). Die Endothelin-1-Konzentrationen waren bei Retinitis-pigmentosa-Patienten ohne Flammer-Syndrom zwischen 1,00–1,20, mit einem Mittelwert (± SD) von 1,10 (± 0,08). Bei gesunden Probanden waren die Werte zwischen 0,90 bis 2,13, der Mittelwert war 1,56 (± 0,30). Retinitis-pigmentosa-Patienten mit höheren Endothelin-1-Konzentrationen hatten Symptome und Zeichen des Flammer-Syndroms, wie z. B. kalte Hände und/oder Füße, niedriger Blutdruck, reduziertes Durstgefühl, allgemein eine erhöhte Empfindlichkeit, wie z. B. erhöhte Schmerzempfindlichkeit und erhöhte Empfindlichkeit auf gewisse Medikamente, gutes Riechvermögen. Schlussfolgerung: Unsere Studie bestätigt frühere Berichte über erhöhte Endothelin-1-Plasmaspiegel bei Retinitis-pigmentosa-Patienten. Die Befunde weisen darauf hin, dass Endothelin-1 besonders dann erhöht ist, wenn die Retinitis-pigmentosa-Patienten gleichzeitig ein Flammer-Syndrom haben. Welche Rolle das Flammer-Syndrom bei Retinitis-pigmentosa-Patienten spielt, muss in zukünftigen Studien noch geklärt werden.

Schlüsselwörter

Endothelin-1-Plasmaspiegel - Flammer-Syndrom - Augendurchblutung - Retinitis pigmentosa - primäre vaskuläre Dysregulation

Key words

endothelin-1 plasma level - Flammer syndrome - ocular blood flow - retinitis pigmentosa - primary vascular dysregulation

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