Our research aims to advance understandings as to how genetic factors, environmental stresses and immune-inflammatory responses effect development, aging and repair capacity of ocular tissues. To this end, the laboratory uses the zebrafish Danio rerio, a vertebrate model for hereditary ocular diseases with remarkable regenerative responses, as well as human ocular biomaterials for the translational research. Applying innovative multidisciplinary approaches that combine biocomputational modelling with proteomics, transcriptomics, genomics, and in vivo cell biology on zebrafish disease models we aim to identify early biomarkers for pathological states as well as therapeutic targets for aiding regenerative responses.
Integrated light-damage models to investigate age-related macular degeneration and regenerative strategies
Excessive or incorrect exposure to light has been associated with retinal degenerative events similar to age-related macular degeneration (AMD) as well as to the development of multisystemic diseases such as dry eye, ocular inflammation and cataract. Unlike mammals, zebrafish has a remarkable ability to spontaneously regenerate both the retina and the retinal pigment epithelium after damage caused by prolonged light exposure. Aim of this research, carried out in collaboration with the laboratory of Rita Maccarone (University of L'Aquila), is to take advantage of the murine and zebrafish model of retinal macular degeneration and regeneration following light exposure, to identify and characterize potential therapeutic targets for AMD.
Lens epithelial cells (LEC) as potential biomarkers of disease
LECs can self-renew and differentiate in the lens fiber cells and play a trophic and protective role ensuring the normal physiological function of the eye throughout life. Risk factors such as ultraviolet radiation, inflammation and the presence of ocular or systemic diseases can impair LEC’s health, triggering pathological events such as cataract and chronic inflammatory response. This research has started at the DJ Apple Laboratory in collaboration with Gerd U. Auffarth (Heidelberg University Hospital) and exploits LECs from cataract surgery in combination with the zebrafish model, to study LEC behaviours and identify biomarkers and/or risk factors for disease states. The laboratory now aims to establish synergies with Ophthalmology centers and clinicians in Italy to foster advancements in this area of research.
Validation of gene therapies for the treatment of congenital thrombotic thrombocytopenic purpura (cTTP)
This is a collaborative effort with the laboratory of Susanna Tomasoni, Mario Negri - IRCCS Bergamo. CTTP is a severe rare disease caused by a biallelic mutation in the ADAMTS13 gene. This deficiency causes formation of spontaneous microthrombi with potential irreversible damage especially of the kidney and brain. Rare ocular manifestations include retinal haemorrhage and corneal vascular occlusions. The Tomasoni's laboratory is currently developing a stem cell-based therapy for restoring the functionality of the ADAMTS13 protein in the blood. The molecular and cellular ophthalmology laboratory contributes to the development of an experimental platform to test the efficacy of therapeutic treatment in a zebrafish disease-model for cTTP.
Motivated scientists at any level are more than welcome to apply. Substantial help for research and raising funds (fellowships etc.) will be provided
- Gerd U Auffarth, The David J Apple International Laboratory of Ocular Pathology and IVCRC, University-Eye Clinic Heidelberg - LECs from cataract surgery
- Silvia Bertoluzza, IMATI, CNR Pavia - Biocomputational modelling of LECs
- Elfriede Friedmann, Institute of Mathematics, University of Kassel - Mathematical models of adult neurogenesis in the zebrafish retina
- Rita Maccarone, Scienze cliniche applicate e biotecnologiche, Università dell’Aquila - Animal models of macular degeneration
- Susanna Tomasoni, Laboratorio Terapia Genica e Riprogrammazione Cellulare, Istituto di Ricerche Farmacologiche Mario Negri – IRCCS Bergamo - TTP gene therapy and cellular reprogramming
- Antonella Sidoti, Rosalia D’Angelo, Luigi Donato, Dipartimento di Scienze biomediche, odontoiatriche e delle immagini morfologiche e funzionali - Transcriptomic profiling in the retina and retinal pigment epithelium
- Matthias Carl, CIBIO, University of Trento - Zebrafish disease models
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