CNR - Institute of Neuroscience CNR
Institute of Neuroscience
 

Project

Study of the functional organization of the mammalian retina - Cell biology of inherited photoreceptor degeneration

Methods: Combination of neuroanatomical techniques. Electron microscopy, confocal microscopy, immunocytochemistry, tract-tracing techniques, single-cell injections, quantitative image analysis. Western blot

Functional architecture of the normal and diseased retina

 

The retina is one of the best-known areas of the Central Nervous System: thanks to modern anatomical techniques, each retinal neuronal type has been identified morphologically; in addition, the highly ordered structure of the retina makes it a privileged site for correlations between structure and function.

Our research is dedicated to the understanding of the functional organization of the mammalian retina; we are also studying the disruption of the retinal fine architecture caused by degenerative diseases that kill photoreceptors, such as Retinitis Pigmentosa (RP). This is a family of inherited disorders causing blindness in approximately 1: 3.500 people.

There is no cure for RP. However, strategies to repair the diseased retina are actively experimented in many laboratories worldwide. Their success depends also from our understanding of the reactions of surviving retinal cells to the death of photoreceptors. Surviving retinal cells, in fact, are often the main target of repair therapies.

Our studies of mouse models of RP have revealed that cells postsynaptic to photoreceptors undergo profound modifications following the death of rods and cones: bipolar and horizontal cells progressively retract their dendrites, loose neurotransmitter receptors, change shape, and eventually die out. These findings have to be taken into account when therapeutic strategies are designed to cure retinal degeneration.

At present we are trying to understand the mechanisms by which retinal remodelling in disease is triggered by the death of photoreceptors. We are also investigating whether it is possible to slow down photoreceptor death in animal models of retinal degeneration by interfering with the apoptotic cascade.

Major scientific contributions:

My major contribution to the understanding of the retinal organization has been the complete reconstruction of the rod pathway, that is the particular chain of neurons carrying through the retina electric signals generated in rod photoreceptors.

 

Also, I have identified general aspects of the anatomical and functional organization of the retina that are highly conserved across different mammalian species.

This project is currently funded by the National Eye Institute of the National Institute of Health (NIH), USA.

In a different set of projects, I am studying the possibility to rescue photoreceptors from degeneration by interfering with the cellular mechanisms of apoptosis. This is a multidisciplinary research in collaboration with Riccardo Ghidoni, from the University of Milan, and Claudia Gargini, from the University of Pisa.

Finally, my laboratory is testing the possibility to employ environmental enrichment as a non invasive tool to enhance photoreceptor viability and survival in inherited photoreceptor degeneration.

Publications

  • Baba K, Pozdeyev N, Mazzoni F, Contreras-Alcantara S, Liu C, Kasamatsu M, Martinez-Merlos T, Strettoi E, Iuvone PM, Tosini G (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.
  • Mazzoni F, Novelli E, Strettoi E (2008) Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J. Neurosci. 28:14282-92.
  • Lin B, Masland RH, Strettoi E (2009) Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp. Eye Res. 88:589-99.
  • Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E (2008) Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J. Neurosci. 28:4878-87.
  • Terzibasi E, Calamusa M, Novelli E, Domenici L, Strettoi E, Cellerino A (2009) Age-dependent remodelling of retinal circuitry. Neurobiol. Aging 30:819-28.
  • Oh EC, Khan N, Novelli E, Khanna H, Strettoi E, Swaroop A (2007) Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL. Proc. Natl. Acad. Sci. U.S.A. 104:1679-84.
  • Gargini C, Terzibasi E, Mazzoni F, Strettoi E (2007) Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J. Comp. Neurol. 500:222-38.
  • Strettoi E, Mears AJ, Swaroop A (2004) Recruitment of the rod pathway by cones in the absence of rods. J. Neurosci. 24:7576-82.
  • Pignatelli V, Strettoi E (2004) Bipolar cells of the mouse retina: a gene gun, morphological study. J. Comp. Neurol. 476:254-66.
  • Pignatelli V, Cepko CL, Strettoi E (2004) Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis. J. Comp. Neurol. 469:351-9.

Grants

2001-2010: National Eye Institute, National Institute of Health (NIH), USA. R01 12654. Inner retinal Neurons in normal and degenerating mice - Principal Investigator

2007-2009: British Retinitis Pigmentosa Society, London, England. Targeting ceramide synthesis to prevent photoreceptor degeneration in Retinitis Pigmentosa - Coordinator

2007-2009: CNR-RSTL. Environmental enrichment as a therapeutic tool to delay photoreceptor degeneration - Principal Investigator

2007-2009: Italian Ministry of research. PRIN 2007. Antiapoptotic strategies in retinal degeneration - Responsible for the CNR unit

Collaborations

  • Connie Cepko, Department of Genetics, Harvard Medical School, Boston, USA.
  • William Hauswirth, University of Gainesville, Florida, USA.
  • Claudia Gargini, Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa.
  • Riccardo Ghidoni, Polo Biomedico Ospedale Sant Paolo, Università di Milano.

 

PI photo

Enrica Strettoi

Contact information

email  E-mail

email  +39 050 3153 213

Participating staff

Elena Novelli

Ilaria Barone

Devid Damiani