Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina

Autor: Stéphanie Lecaudé, Ute E. K. Wolf-Schnurrbusch, Sylvie Eigeldinger-Berthou, Volker Enzmann, Rahel Zulliger
Rok vydání: 2011
Předmět:
Zdroj: Zulliger, Rahel; Lecaudé, Stéphanie; Eigeldinger-Berthou, Sylvie; Wolf-Schnurrbusch, Ute; Enzmann, Volker (2011). Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina. Graefe's archive for clinical and experimental ophthalmology, 249(6), pp. 859-869. Berlin: Springer-Verlag 10.1007/s00417-010-1584-6
Graefes Arch Clin Exp Ophthalmol.
ISSN: 1435-702X
0721-832X
DOI: 10.1007/s00417-010-1584-6
Popis: Background: Retinal degeneration is followed by significant changes in the structure and function of photoreceptors in humans and several genetic animal models. However it is not clear whether similar changes occur when the degeneration is induced pharmacologically. Therefore our aim was to investigate the influence of retinotoxic N methyl Nnitrosourea (MNU) on the function morphology and underlying molecular pathways of programmed cell death. Methods: C57/BL6 mice were injected with different doses of MNU and function was determined by analysing optokinetic reflex measurements and cued water maze results at several time points post injection. Morphometric measurements were also taken from HE stained paraffin eye sections. TUNEL positive cells and caspase 3 and 6 were detected by immunohistochemistry. To assess the molecular changes leading to cell death qRT PCR from neurosensory retina mRNA was performed. Results: The application of MNU led to an instant decrease in function and a delayed decrease in the thickness of the retinal outer nuclear layer. These responses were observed in the absence of any structural changes in the retinal pigment epithelium. The degeneration of the photoreceptor cell layer was highest with 60 mg/kg MNU. The assessment of TUNEL positive cells visualised cell death after treatment but no detectable caspase 3 activity was observed concomitant with these changes. qRT PCR revealed the possible involvement of the inflammatory mediator caspase 1 and endoplasmic reticulum stress mediated apoptosis by caspase 12. Conclusion: MNU leads to the dose dependent degeneration of photoreceptor cells in mice by caspase 3 independent pathways and is therefore a suitable model to study retinal degeneration in an animal model.
Databáze: OpenAIRE
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