April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Inhibition of Ceramide de novo Synthesis in an Animal Model of Retinitis Pigmentosa: II. Effects on Photoreceptor Survival and Function
Author Affiliations & Notes
  • M. Gargini
    Psychiatry & Neurobiology, University of Pisa, Pisa, Italy
  • A. Asta
    Psychiatry & Neurobiology, University of Pisa, Pisa, Italy
  • I. Piano
    Psychiatry & Neurobiology, University of Pisa, Pisa, Italy
  • P. Gasco
    Nanovector srl, Turin, Italy
  • C. Musicanti
    Nanovector srl, Turin, Italy
  • E. Novelli
    Bietti Foundation, Rome, Italy
  • E. Strettoi
    Neuroscience Institute CNR, Pisa, Italy
  • R. Ghidoni
    DIMCO, San Paolo Medical School, Milan, Italy
  • Footnotes
    Commercial Relationships  M. Gargini, Inventor, P; A. Asta, None; I. Piano, None; P. Gasco, Nanovector srl, Turin, Italy, E; Nanovector srl, Turin, Italy, P; Nanovector srl, Turin, Italy, R; C. Musicanti, Nanovector srl Turin, Italy, E; E. Novelli, None; E. Strettoi, Inventor, P; R. Ghidoni, Inventor, P.
  • Footnotes
    Support  MIUR, PRIN 2007 (MCG) ; BRPS (ES); R01 EY 12654 (ES)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4463. doi:
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      M. Gargini, A. Asta, I. Piano, P. Gasco, C. Musicanti, E. Novelli, E. Strettoi, R. Ghidoni; Inhibition of Ceramide de novo Synthesis in an Animal Model of Retinitis Pigmentosa: II. Effects on Photoreceptor Survival and Function. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4463.

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

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Purpose: : In the companion paper, we show that ceramide biosynthesis plays a role in the apoptotic pathway leading to photoreceptor death in a mouse model of Retinitis Pigmentosa (RP). Here, we attempt to slow down photoreceptor degeneration in the same mutant by chronic administration of inhibitors of serine palmitoyltransferase (SPT), the enzyme that catalyzes the limiting step of ceramide biosynthesis. We use a nanotechnology- based preparation to deliver drugs to the retina of rd10 mutant mice, later assessing retinal preservation and functional performance by means of histology and ERG recordings.

Methods: : Mice of the rd10 strain were used. These carry a missense mutation of the rod-specific phosphodiesterase leading to a degeneration of photoreceptors from P14 rd10 animals aged P14 to P35 were administered daily eye drop formulation of SPT inhibitors loaded into Solid Lipid Nanoparticles (SLN) obtained from warm microemulsion (Nanovector srl, Italy). Control mice were given unloaded lipid particles. Scotopic and photopic ERG recordings were obtained from animals of various ages (P20; P25; P30; P35). Retinal sections from ERG recorded animals were stained with nuclear dyes and examined at a confocal microscope for measurements of the photoreceptor layer thickness.

Results: : Chronic administration of SPT inhibitors and of unloaded SLN formulation did not cause adverse local or general effects. ERG responses could be evoked from treated rd10 mice even after complete ERG extinction in untreated, control animals. Scotopic a-waves were recordable from untreated mice only in the P20-P22 window but persisted clearly even after P30 in treated littermates. Histological examination of treated and untreated retinas at P24 (the peak of rod apoptosis in this strain) showed prolonged survival of photoreceptors with a higher number of nuclei rows in the outer nuclear layer.

Conclusions: : Non invasive, chronic administrations of nanoparticle loaded SPT inhibitors are effective in slowing down photoreceptor death and preserving the ERG response in a known mouse model of RP. This is particularly relevant in view of the fact that typical RP has a naturally slow evolution; a strategic way to attack this disease is to further delay the degeneration of photoreceptors, and particularly the secondary death of cones, the only cells upon which residual vision is based in RP patients.

Keywords: electroretinography: non-clinical • apoptosis/cell death • transgenics/knock-outs 

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