Senior research scientist
Via Giuseppe Moruzzi, 1
56124 - Pisa
Retinal neurobiology in health and disease
The retina is one of the best-known areas of the Central Nervous System: thanks to modern morphological techniques targeting single neuronal types, the full catalogue of cells (the retinal “neurome”) has been identified for mammalians and the general constitutive plan of this outpost of the brain shown to be highly conserved among Vertebrates. The highly ordered structure of the retina makes it a privileged site for correlations between structure and function so that this organ is studied for its role in vision as well as a paradigm of approachable portion of the CNS to understand its development, physiological properties and response to treatments.
Moreover, retinal diseases often lead to severe visual impairment with high human and economic consequences: this solicits strong investments in basic and applied retinal research worldwide in the attempt to prevent or reduce blindness.
Functional organization of the mammalian retina
Our research is partly dedicated to the understanding of the functional organization of the normal mammalian retina; we are interested in learning what particular types of neurons are dedicated to specific tasks and what are the consequences of interfering (i.e. by means of genetic manipulations) with their normal development. Examples are studies dedicated to the interactions between rods and cones; to the organization of types of bipolar cells contributing differently to the scotopic and photopic pathways; to the role of ganglion cells in shaping retinal circuitry.
In the years, we have been able to identify general aspects of the anatomical and functional organization of the retina that are highly conserved across different mammalian species and represent a true blueprint.
Neurobiology of inherited photoreceptor degeneration
A large fraction of our research is dedicated to exploit animal models of Retinitis Pigmentosa (RP) to understand the pathophysiology of this disease and also to design experimental rescue strategies. RP constitutes a family of inherited disorders causing blindness in approximately 1: 3.500 people. Typically, a mutation (which might be in a photoreceptor-specific gene) leads to the primary degeneration of rods, with consequent night blindness. For still poorly understood reasons, a secondary death of cones occurs, ultimately causing loss of daylight, hi-acuity vision up to legal blindness. Our laboratory has played a relevant role in understanding numerous of the secondary, regressive events slowly propagating to the inner retina, in a process called “remodelling”, which might put to risk repair strategies designed to restore vision.
Because of the dying retinal cells are CNS neurons, and also as a consequence of remodelling and of the high genetic heterogeneity of RP, the possibilities of curing this disease are very limited. However, strategies for retinal repair are actively experimented in many laboratories worldwide and the last decade has experienced tremendous progresses in the field. An important concept is that “sparing the rods, saves the cones”: hence, a simple delay of the primary degeneration of rods can produce a proportionally higher benefit due to a positive effect on cones.
Our effort is to contribute making a cure for RP closer, focussing on these objectives:
- To identify common features of retinal remodelling in paradigms of RP caused by different mutations. The reaction of surviving retinal cells to the death of photoreceptors is crucial, since surviving cells are often the main target of repair therapies, such as optogenetics.
- To exploit rescue therapies based on manipulations of the environment (Environmental Enrichment) to slow down photoreceptor degeneration, enhancing the endogenous defence response of the retina.
- To implement rescue therapies based upon pharmacological tools administered to the eye and targeting selective apoptotic pathways, involved in the primary death of photoreceptors.
Laboratory organization and experimental approach
Our research is based on a combination of methods usually beginning with morphological observations and then extend to include biochemical, behavioural, electrophysiological and molecular studies. This multidisciplinary strategy is made possible also by consolidated collaborations with intramural and extramural scientists.
Most recently used approaches comprise: confocal microscopy; image analysis; immunocytochemistry; transmission electron microscopy; immuno-EM; gene-gun dyolistic labelling; western blot; ERG recordings; visual behaviour; qRT-PCR etc.
The laboratory has an international reputation for retinal neurobiology studies and a consolidated network of collaborations with Italian and foreign Inìstitutions.
Piano I, Novelli E, Gasco P, Ghidoni R, Strettoi E, Gargini C.
Cone survival and preservation of visual acuity in an animal model of retinal degeneration. Eur J Neurosci. 2013 Jun;
Barone I, Novelli E, Piano I, Gargini C, Strettoi E.
Environmental enrichment extends photoreceptor survival and visual function in a mouse model of retinitis pigmentosa.
PLoS One. 2012;7(11):e50726.
Damiani D, Novelli E, Mazzoni F, Strettoi E.
Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: a paradigm of early onset
photoreceptor degeneration. J Comp Neurol. 2012 May 1;520(7):1406-23.
Pang JJ, Dai X, Boye SE, Barone I, Boye SL, Mao S, Everhart D, Dinculescu A, Liu L, Umino Y, Lei B, Chang B, Barlow R, Strettoi E, Hauswirth WW.
Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse,
a model of recessive retinitis pigmentosa. Mol Ther. 2011 Feb;19(2):234-42.
Strettoi E, Gargini C, Novelli E, Sala G, Piano I, Gasco P, Ghidoni R.
Inhibition of ceramide biosynthesis preserves photoreceptor structure and function in a mouse model
of retinitis pigmentosa. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18706-11.
Strettoi E, Novelli E, Mazzoni F, Barone I, Damiani D.
Complexity of retinal cone bipolar cells. Prog Retin Eye Res. 2010 Jul;29(4):272-83.
Mazzoni F, Novelli E, Strettoi E.
Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited
photoreceptor degeneration. J Neurosci. 2008 Dec 24;28(52):14282-92.
Recent extramural grants
2013-2016: Principal Investigator of the Project “Sphingolipid ceramide signaling in retinal degeneration: in vivo targeting” funded by the Macula Vision Research Foundation, Pennsylvania, USA. In collaboration with C Gargini and R. Ghidoni.
2011-2013: Principal Investigator of the Project "Environmental Enrichment: a new, non invasive approach, to slow down photoreceptor degeneration in Retinitis Pigmentosa funded by the Velux Stiftung Foundation, Switzerland.
2013-2015: Investigator in a Unit of The National Interest Research Project “Integrated analysis of molecular and cellular processes responsible for elaborating sensory communication in normal and pathological conditions” funded by the Italian Ministry of Research and University (PRIN Project). National coordinator: A. Menini. Responsible for the University of Pisa Unit: MC Gargini. In collaboration with MC Gargini and R. Ghidoni.
2007-2010: Unit head of The National Interest Research Project ”Anti-apoptotic strategies in retinal degenerations” funded by the Italian Ministry of Research and University (PRIN Project). National coordinator: MC Gargini.
2007-2009: Responsible for the Curiosity Driven Project (RSTL) “Environmental Enrichment as a therapeutic tool for retinal degenerations” funded by the Italian National Research Council (CNR).
2007-2009: Principal investigator of the Project “Targeting ceramide signaling to prevent photoreceptor degeneration” funded by the British Retinis Pigmentosa Society, London. In collaboration with MC Gargini and R. Ghidoni.
2001-2010: Principal Investigator. Project “Inner retinal neurons in normal and degenerating mice” (R01 EY12654) funded by the National Eye Institute, National Institute of Health (NIH, USA).
Matteo Caleo, CNR Neuroscience Institute, Pisa
Lucia Galli, CNR Neuroscience Institute, Pisa
Claudia Gargini, Department of Pharmacy, University of Pisa, Italy
Riccardo Ghidoni, St. Paolo Hospital Medical School, University of Milan, Italy
William Hauswirth, College of Medicine,University of Gainesville, Florida, USA
Gianluca Tosini, Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, USA