The primary objective of this study is to assess the morphological and functional integrity of the inner retina in mouse models of Retinitis Pigmentosa (RP). RP comprises a group of inherited disorders characterized by progressive degeneration of retinal photoreceptors, and represents one of the major causes of blindness in the world, with no available cure. The most promising strategies to treat this devastating disease include gene therapy, the electrical stimulation of the inner retina with artificial prostheses and cellular transplantation. Their success is partly based upon the assumption that the inner retina is largely preserved following photoreceptor death and that adverse effects upon residual cells are very limited. However, recent literature has provided clear evidence of negative retinal remodeling in animal models of RP: inner retinal cells undergo severe morphological and functional alterations that become evident only when selective methods of investigation (such as the visualization of individual cells) are used. ? Our long-term objective is to identify the exact time sequence and mechanisms by which photoreceptor degeneration triggers adverse effects upon other retinal cells, ultimately to prevent them completely and to recognize optimal time windows for rescue therapies. ? The present project is based upon anatomical, electrophysiological and developmental studies of the retinal organization in unique mouse models of RP, which reproduce some of the most frequent forms of the human disease. Modern techniques are combined to reveal morphological and functional abnormalities of inner retinal cells at various stages of the disease progression. Human retinas from postmortem RP donors are also examined microscopically.
We aim at uncovering inner retinal abnormalities that are common to both mouse and human forms of retinal degeneration and occur independently of the underlying genetic cause. This is very important to design mutation-independent therapies. ? ? ?

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CB-G (90))
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Mariani, Andrew P
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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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