PROinsulin Cpeptide protects eyesight aka Proinsulin attenuates the loss of vision and delays apoptosis of photoreceptors in a mouse model of retiniti

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Proinsulin attenuates the loss of vision and delay...[Invest Ophthalmol Vis Sci. 2008] - PubMed Result

Invest Ophthalmol Vis Sci. 2008 May 30. [Epub ahead of print]Links

Proinsulin attenuates the loss of vision and delays apoptosis of photoreceptors in a mouse model of retinitis pigmentosa.

Corrochano S, Barhoum R, Boya P, Arroba AI, Rodriguez-Muela N, Gomez-Vicente V, Bosch F, de Pablo F, de la Villa P, de la Rosa EJ.

Cellular and Molecular Physio pathology, CIB-CSIC, Madrid, Spain.

PURPOSE: Retinitis pigmentosa (RP) is a heterogeneous group of inherited conditions that lead to blindness and for which there is no effective therapy. Apoptosis of photoreceptors is a common feature in animal models of the disease. Thus, we have studied the therapeutic potential of proinsulin, an anti-apoptotic molecule that is active during retinal development. METHODS: Transgenic mice expressing human proinsulin (hPi) in the skeletal muscle were generated in a mixed C57BL/6:SJL background and back-crossed to a C57BL/6 background. Two independent lineages of transgenic mice were established, in which hPi production in muscle was constitutive and not regulated by glucose levels. hPi levels in serum, muscle and retina were determined with a commercial ELISA kit, visual function was evaluated by electroretinogram (ERG) recording and programmed cell death was assessed by TUNEL. Immunohistochemistry was used to evaluate retinal structure preservation and oxidative damage. RESULTS: Transgenic expression of hPi in the rd10 retinal degeneration mouse model led to prolonged vision, as determined by ERG recording, in a manner that was related to the level of transgene expression. This attenuation of visual deterioration was correlated with a delay in photoreceptor apoptosis, as well as with the preservation of retinal cytoarchitecture, particularly that of the cones. CONCLUSIONS: Our results provide a new basis for possible therapies to counteract retinitis pigmentosa, as well as a new tool to dissect out the mechanisms involved in the progress of retinal neurodegeneration.

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