Director of research
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 Institutions.
Stefanov A, Novelli E, Strettoi E. Inner retinal preservation in the
photoinducible I307N rhodopsin mutant mouse, a model of autosomal dominant
retinitis pigmentosa. J Comp Neurol. 2019 Dec 6. d
Testa G, Mainardi M, Morelli C, Olimpico F, Pancrazi L, Petrella C, Severini
C, Florio R, Malerba F, Stefanov A, Strettoi E, Brandi R, Arisi I, Heppenstall P,
Costa M, Capsoni S, Cattaneo A. The NGF(R100W) Mutation Specifically Impairs
Nociception without Affecting Cognitive Performance in a Mouse Model of
Hereditary Sensory and Autonomic Neuropathy Type V. J Neurosci. 2019 Dec
Falasconi A, Biagioni M, Novelli E, Piano I, Gargini C, Strettoi E. Retinal
Phenotype in the rd9 Mutant Mouse, a Model of X-Linked RP. Front Neurosci. 2019
Guadagni V, Biagioni M, Novelli E, Aretini P, Mazzanti CM, Strettoi E.
Rescuing cones and daylight vision in retinitis pigmentosa mice. FASEB J. 2019
Strettoi E, Masri RA, Grünert U. AII amacrine cells in the primate fovea
contribute to photopic vision. Sci Rep. 2018 Nov 6;8(1):16429.
Guadagni V, Novelli E, Piano I, Gargini C, Strettoi E., Pharmacological approaches to retinitis pigmentosa: A laboratory perspective. Prog Retin Eye Res.2015 Sep;48:62-81. doi: 10.1016/j.preteyeres.2015.06.005.
2015-2019: Italian Partner, scientific responsible of the international project “SwitchBoard - In the Eye of the Observer: Visual Processing at the Heart of the Retina”. Innovative Training Network (ITN), funded within the Horizon 2020 EU initiative through the Marie Sklodowska-Curie grant agreement No 674901.
Coordinator: Thomas Euler, University of Tubingen, Germany. Participants: 8 academic, research and industrial partners from 8 Countries.
2015-2018: Head of the multicentric project “Slowing down Retinitis Pigmentosa with a mutation-independent approach: in vivo assessment on multiple animal models” funded by Fondazione Roma, “Retinite Pigmentosa” call. Units Heads: Claudia Gargini (University of Pisa) and Riccardo Ghidoni (University of Milan)
2013-2018: 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 Claudia Gargini (University of Pisa) and Riccardo Ghidoni (University of Milan).
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.
2001-2005; 2006-2010: Principal Investigator, Foreign Institute. Projects “Inner retinal neurons in normal and degenerating mice” (R01 EY12654-2R01 EY12654) funded by the National Eye Institute, National Institute of Health (NIH, USA).
Claudia Gargini, Department of Pharmacy, University of Pisa, Italy
Antonino Cattaneo, Scuola Normale Superiore, Pisa
Simona Capsoni, University of Ferrara
Stanislao Rizzo, Policlinico Gemelli, Rome
Strettoi's biography (28 october 2019)