Zusammenfassung
Hintergrund: Nach einer traumatischen Läsion des Sehnervs kommt es zu einer progressiven Degeneration
von retinalen Ganglienzellen (RGZ) durch Apoptose und damit einem Verlust der Sehfähigkeit
des betroffenen Auges. Wie auch andere Neurone des zentralen Nervensystems können
die RGZ ihre geschädigten Axone nicht spontan regenerieren. Wir setzten spezielle
chirurgische und pharmakologische Methoden ein, um das Überleben der RGZ und die Regeneration
ihrer Axone zu erreichen. Material und Methoden: Die Untersuchungen fanden am Modell der Degeneration der RGZ nach einer Schädigung
des Sehnervs der adulten Ratte statt. Die RGZ wurden mit einem Fluoreszenzfarbstoff
beladen und verschiedene Substanzen wurden intravitreal appliziert. Nach zwei Wochen
wurden die Effekte anhand der Anzahl der überlebenden RGZ quantifiziert. Für die Untersuchungen
zur Regeneration wurde an den Stumpf des Sehnervs ein autologes peripheres Transplantat
angenäht oder die beiden Enden des durchtrennten Sehnervs wurden wieder zusammengenäht.
Die Wiederherstellung der Funktion der RGZ wurde mittels VEP-Messungen untersucht.
Ergebnisse: Die Anzahl der eine Axotomie überlebenden RGZ stieg signifikant nach intravitrealen
Injektionen von Aurintricarboxylsäure, Cortisol, eines Caspase-Hemmers, Brimonidin
oder Mikroglia-gerichteter Substanzen an. Die Regeneration der durchtrennten Axone
konnte durch Aurintricarboxylsäure oder Cortisol verstärkt werden. Erhebliche neuroprotektive
und regenerative Effekte einschließlich einer partiellen Wiederherstellung des VEP
konnten durch die Induktion einer Linsenverletzung, welche zu einer allmählichen Freisetzung
von Kristallinen in den Glaskörper führt, oder durch die intravitreale Injektion von
aufgereinigten Kristallinen erreicht werden. Schlussfolgerung: Durch geeignete neuroprotektive Maßnahmen kann der bislang unvermeidliche Verlust
der Sehfähigkeit nach einem Sehnervtrauma im Tiermodell verhindert werden, was die
Entwicklung von Behandlungsmethoden für Patienten hoffnungsvoll erscheinen lässt.
Abstract
Background: After a traumatic lesion of the optic nerve, retinal ganglion cells (RGC) undergo
massive degeneration by apoptosis, which leads to loss of vision in the affected eye.
Like other neurones in the central nervous system, RGC are not able to regenerate
their damaged axons spontaneously. We used special surgical methods and pharmacological
measures to achieve enhanced survival and regeneration of damaged RGC. Materials and Methods: Studies were performed using the model of RGC degeneration induced by severing the
optic nerve of adult rats. RGC were loaded with a fluorescent dye, and several drugs
were applied intravitreally. The effects were evaluated after two weeks by counting
the surviving RGC. For regeneration studies, an autologous peripheral nerve graft
was sutured to the stump of the cut optic nerve, or the ends of the cut optic nerve
were re-sutured. Recovery of RGC function was assessed by VEP measurements. Results: The number of RGC surviving an axotomy increased significantly after intravitreal
injections of aurintricarboxylic acid, cortisol, a caspase inhibitor, brimonidine
or microglia-targeted substances. Regeneration of cut axons was enhanced by aurintricarboxylic
acid or cortisol. In addition, considerable neuroprotective and regenerative effects
including partial restoration of VEP were induced by lens injury, which results in
a gradual release of crystallins into the vitreous, or by intravitreal injection of
purified crystallins. Conclusion: The loss of vision after an optic nerve trauma can be reduced in this animal model
by suitable neuroprotective measures, which raises hope for the treatment of patients.
Schlüsselwörter
Retinale Ganglienzellen - Trauma - Sehnerv - Apoptose - Neuroprotektion - Regeneration
- Aurintricarboxylsäure - Linsenverletzung - Kristallin - VEP
Key words
Retinal ganglion cells - trauma - optic nerve - apoptosis - neuroprotection - regeneration
- aurintricarboxylic acid - lens injury - crystallin - VEP
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