Overview

Vision is one of the most essential human senses and relies on proper retinal function. Mutations in retinal genes are generally non-lethal but can cause severe, disabling inherited retinal dystrophies (IRDs), such as retinitis pigmentosa, characterized by progressive photoreceptor degeneration. IRDs represent a leading cause of blindness worldwide, and for the vast majority of these conditions, no effective cure is currently available. Although many disease-associated genes have been identified, the molecular mechanisms driving photoreceptor degeneration remain incompletely understood. Therefore, there is a critical need to develop reliable experimental models that accurately recapitulate the underlying pathogenic mechanisms and that can serve as platforms for the identification and testing of novel therapeutic strategies. Retina

Research directions

Our laboratory studies the factors driving the differentiation and survival of retinal neurons. We aim to identify the mechanisms that maintain retinal function, and how these can be disrupted in pathological conditions. For this, we use a multidisciplinary approach, from three-dimensional cell cultures to genetic models.

Current efforts focus on the characterization of a novel zebrafish model of Retinitis pigmentosa, caused by mutations in IMPG2, a photoreceptor-specific proteoglycan. We are also using our model in a medium-throughput screen to search for new therapeutic leads.

Group members

  • Simona Casarosa, PI
  • Alba Cumplido Mayoral, PhD student
  • Michele Tedesco, Pre-doctoral fellow
  • Luigi Balasco, Visiting scientist

Collaborations

  • Michela Denti, University of Trento
  • Yuri Bozzi, University of Trento
  • Federica Romanelli, ASUIT Trento
  • Bice Avallone, Federico II University Naples
  • Marco Schiavone, University of Brescia
  • Chiara Gabellini, University of Pisa
  • Enrica Strettoi, CNR Institute of Neurosciences
  • Jennifer Hocking, University of Alberta Calgary
  • Stephan Neuhauss, University of Zurich

Funding

Bando: PRIN 2022 (D.D. 104/22)
Investigating the role of IMPG2 in retinal dystrophies by molecular, ultrastructural and behavioral analysis of zebrafish mutants
Simona Casarosa, coordinatrice
Codice Protocollo: 2022JSYEAB     CUP: E53D23012160006

Selected publications

Di Leva F, Arnoldi M, Santarelli S, Massonot M, Lemée MV, Bon C, Pellegrini M, Castellini ME, Zarantonello G, Messina A, Bozzi Y, Bernier R, Zucchelli S, Casarosa S, Dassi E, Ronzitti G, Golzio C, Morandell J, Gustincich S, Espinoza S, Biagioli M. (2025). SINEUP RNA rescues molecular phenotypes associated with CHD8 suppression in autism spectrum disorder model systems. Mol Ther. doi: 10.1016/j.ymthe.2024.12.043

Brighenti T, Neri G, Mazzola M, Tomé G, Scalfati M, Peroni D, Belli R, Zampedri E, Tebaldi T, Borello U, Romanelli F, Casarosa S (2024). Comparative proteomic analysis of human vitreous in rhegmatogenous retinal detachment and diabetic retinopathy reveals a common pathway and potential therapeutic target. Clin Proteomics. doi: 10.1186/s12014-024-09515-3

Castellini ME, Spagnolli G, Poggi L, Biasini E, Casarosa S, Messina A. (2023). Identification of the zebrafish homologues of IMPG2, a retinal proteoglycan. Cell Tissue Res. doi: 10.1007/s00441-023-03808-z.

Gilmozzi V, Gentile G, Riekschnitz DA, Von Troyer M, Lavdas AA, Kerschbamer E, Weichenberger CX, Rosato-Siri MD, Casarosa S, Conti L, Pramstaller PP, Hicks AA, Pichler I, Zanon A. (2021). Generation of hiPSC-Derived Functional Dopaminergic Neurons in Alginate-Based 3D Culture. Front Cell Dev Biol. 9:708389. doi: 10.3389/fcell.2021.708389. eCollection 2021.

Karali M., Guadagnino I., Marrocco E., De Cegli R., Carissimo A., Pizzo M., Casarosa S., Conte I., Surace E.M., Banfi S. (2019). AAV-miR-204 protects from retinal degeneration by attenuation of microglia activation and photoreceptor cell death. Molecular Therapy 19:144-156. doi: 10.1016/j.omtn.2019.11.005. Epub 2019 Nov 18.

Zhang X, Piano I, Messina A, D'Antongiovanni V, Crò F, Provenzano G, Bozzi Y, Gargini C, Casarosa S. (2019). Retinal Defects in Mice Lacking the Autism-Associated Gene Engrailed-2. Neuroscience. Apr 10. pii: S0306-4522 (19) 30236-2. doi: 10.1016/j.neuroscience.2019.03.061. [Epub ahead of print] 

Chelini G, Zerbi V, Cimino L, Grigoli A, Markicevic M, Libera F, Robbiati S, Gadler M, Bronzoni S, Miorelli S, Galbusera A, Gozzi A, Casarosa S, Provenzano G, Bozzi Y. (2019). Aberrant somatosensory processing and connectivity in mice lacking Engrailed-2. J Neurosci. 39:1525-1538. doi: 10.1523/JNEUROSCI.0612-18.2018