June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
A rat model of retinal degeneration induced by intraocular injections of CNF1 toxin
Author Affiliations & Notes
  • Enrica Strettoi
    CNR Neuroscience Institute, Pisa, Italy
  • Viviana Guadagni
    CNR Neuroscience Institute, Pisa, Italy
  • Chiara Cerri
    CNR Neuroscience Institute, Pisa, Italy
  • ilaria piano
    GB Bietti Foundation for Ophthalmology, Rome, Italy
  • Antonella Caputo
    Pharmacy, University of Pisa, Pisa, Italy
  • Elena Novelli
    GB Bietti Foundation for Ophthalmology, Rome, Italy
  • Carla Fiorentini
    Istituto Superiore di Sanità, Rome, Italy
  • Claudia Gargini
    Pharmacy, University of Pisa, Pisa, Italy
  • Matteo Caleo
    CNR Neuroscience Institute, Pisa, Italy
  • Footnotes
    Commercial Relationships Enrica Strettoi, None; Viviana Guadagni, None; Chiara Cerri, None; ilaria piano, None; Antonella Caputo, None; Elena Novelli, None; Carla Fiorentini, None; Claudia Gargini, None; Matteo Caleo, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 725. doi:
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      Enrica Strettoi, Viviana Guadagni, Chiara Cerri, ilaria piano, Antonella Caputo, Elena Novelli, Carla Fiorentini, Claudia Gargini, Matteo Caleo; A rat model of retinal degeneration induced by intraocular injections of CNF1 toxin. Invest. Ophthalmol. Vis. Sci. 2013;54(15):725.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: In rodent models of inherited retinal degeneration, expression of defective genes often begins when development is still completing, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, rodent eyes often turn out to be too small to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable. Starting from the serendipitous observation that intraocular injections of Cytotoxic Necrotizing Factor 1(CNF1) toxin lead to retinal degeneration, we implemented an inducible model recapitulating key features of Retinitis pigmentosa (RP).

Methods: A single intravitreal injection of 0.1, 2, 3, and 10 nM CNF1 was performed in the right eyes of Long Evans hooded rats aged 2-4 months. Left eyes were injected with vehicle. After 2, 7 and 14 days, the eyes were fixed and frozen sections stained with antibodies labeling photoreceptors, bipolar, horizontal, amacrine and ganglion cells and retinal glia, which were studied by confocal microscopy. Additional rats were used to record the flash electroretinogram (ERG) in scotopic and photopic conditions.

Results: 3nM CNF1 was found to be optimal for generating a retinal degeneration pattern displaying key features of RP. One week after CNF1 injection, a clear effect on photoreceptors is observed, with loss of these cells and decrement in the number of inner nuclear layer rows. Reactive gliosis of Muller cells occurs. Bipolar and horizontal cells sprout toward the pigment epithelium while cells from the inner retina migrate in the inner plexiform layer. ERG recordings show a net decrease in the amplitude coherent with photoreceptor loss. At later times, photoreceptor rosettes also form. A dose-dependent effect of CNF1 is observed.

Conclusions: CNF1 is produced by pathological E. choli and causes constitutive activation of Rho-GTPases. These are key regulators of the actin cytoskeleton, highly expressed in photoreceptors, which are very sensitive to their activity (i.e. to Rac1). This explains a preferential effect of intravitreal CNF1 on these retinal cells. Because of the combination of morphological and functional findings described here, we expect that the adopted experimental paradigm will contribute to develop an inducible model of retinal degeneration instrumental to basic biology studies and rescue approaches.

Keywords: 695 retinal degenerations: cell biology • 702 retinitis • 689 retina: distal (photoreceptors, horizontal cells, bipolar cells)  

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