): The proposed research concerns the morphological organization of the inner retina of the mouse. This is important because of the paucity of information about the mouse retina, at a time when the mouse is gaining increasing relevance as an animal model thanks to the advent of genetic manipulations. We propose to continue a study concerning the identification and quantitative distribution of the major populations of cells in the inner retina of the mouse. We will build an anatomical database that can be used as a base of reference for scientists studying the development and the adult retinal organization in normal and genetically-altered mammals. The outcome of building a database for the retina of the mouse will be immediate: we propose to assess the morphological integrity of inner retinal neurons in mice with inherited photoreceptor degeneration. Possible strategies for treating similar degeneration in humans include photoreceptor transplantation and electronic (prosthetic) stimulation of the retina. They are based upon the assumption that the inner retina is not at all affected by photoreceptor loss, but there is very little experimental evidence that this is indeed true. On the contrary, the existing literature points to a specific loss of inner retinal neurons, which would impair any attempt to restore vision through photoreceptor replacement. Any outcome of this research is useful: if no changes are observed consequent to photoreceptor degeneration in either morphology or overall distribution of single types of inner retinal cells, then it can be concluded that inner retinal changes secondary to photoreceptor are of limited relevance. If selective alterations are identified, they have to be taken into account when devising new therapeutic strategies. They would also become candidates as contributors to the secondary degeneration of cones that follows loss of rods.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences C Study Section (VISC)
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Dudley, Peter A
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Instituto Di Neuroscienze
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Damiani, Devid; Novelli, Elena; Mazzoni, Francesca et al. (2012) Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: a paradigm of early onset photoreceptor degeneration. J Comp Neurol 520:1406-23
Baba, Kenkichi; Mazzoni, Francesca; Owino, Sharon et al. (2012) Age-related changes in the daily rhythm of photoreceptor functioning and circuitry in a melatonin-proficient mouse strain. PLoS One 7:e37799
Sengupta, Anamika; Baba, Kenkichi; Mazzoni, Francesca et al. (2011) Localization of melatonin receptor 1 in mouse retina and its role in the circadian regulation of the electroretinogram and dopamine levels. PLoS One 6:e24483
Strettoi, Enrica; Gargini, Claudia; Novelli, Elena et al. (2010) Inhibition of ceramide biosynthesis preserves photoreceptor structure and function in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci U S A 107:18706-11
Strettoi, Enrica; Novelli, Elena; Mazzoni, Francesca et al. (2010) Complexity of retinal cone bipolar cells. Prog Retin Eye Res 29:272-83
Baba, Kenkichi; Pozdeyev, Nikita; Mazzoni, Francesca et al. (2009) Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor. Proc Natl Acad Sci U S A 106:15043-8
Lin, Bin; Masland, Richard H; Strettoi, Enrica (2009) Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res 88:589-99
Mazzoni, Francesca; Novelli, Elena; Strettoi, Enrica (2008) Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci 28:14282-92
Damiani, Devid; Alexander, John J; O'Rourke, Jason R et al. (2008) Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 28:4878-87
Gargini, Claudia; Terzibasi, Eva; Mazzoni, Francesca et al. (2007) Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol 500:222-38

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