Francesca Simonelli

Professor of Ophtalmology

Name Francesca
Surname Simonelli
Institution Università degli Studi della Campania Luigi Vanvitelli
E-Mail francesca.simonelli@unicampania.it
Address Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
Francesca Simonelli

Member PUBLICATIONS

  • Activation of Melanocortin Receptors MC 1 and MC 5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy.

    Publication Date: 01/01/2016 on Mediators of inflammation
    by Rossi S, Maisto R, Gesualdo C, Trotta MC, Ferraraccio F, Kaneva MK, Getting SJ, Surace E, Testa F, Simonelli F, Grieco P, Merlino F, Perretti M, D'Amico M, Di Filippo C
    DOI: 10.1155/2016/7368389

    We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12-16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 μL) of the selective MC1 small molecule agonist BMS-470539 (33 μmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1β, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment.

  • Evaluation of Ocular Gene Therapy in an Italian Patient Affected by Congenital Leber Amaurosis Type 2 Treated in Both Eyes.

    Publication Date: 01/01/2016 on Advances in experimental medicine and biology
    by Testa F, Maguire AM, Rossi S, Marshall K, Auricchio A, Melillo P, Bennett J, Simonelli F
    DOI: 10.1007/978-3-319-17121-0_71

    Gene therapy clinical trials with gene augmentation therapy for Leber Congenital Amaurosis have shown partial reversal of retinal dysfunction. Most studies described the effect of treatment in a single eye and limited evidence is reported in literature about patients treated in both eyes. In this chapter, we present the findings of a young patient treated in both eyes. Efficacy of the treatment was assessed with Best Corrected Visual Acuity, Goldman Visual Field testing, Esterman computerized binocular visual field and Microperimetric testing. Post-treatment results showed improvement of visual function in both eyes, in particular, a strong amelioration was observed after the first injection, by using conventional monocular tests. Moreover, the treatment in the second eye resulted in a further improvement of binocular visual functionality, as easily detected by computerized binocular visual field. In conclusion, our data suggest that gene therapy can inhibit retinal degeneration and can be safe and effective in restoring visual functionality in young subjects treated in both eyes. Finally, new outcome measurements, in particular binocular computerized visual field parameters, can therefore be useful to quantify overall visual gain in patients undergoing gene therapy in both eyes.

  • Investigation of Aberrant Splicing Induced by AIPL1 Variations as a Cause of Leber Congenital Amaurosis.

    Publication Date: 01/12/2015 on Investigative ophthalmology & visual science
    by Bellingham J, Davidson AE, Aboshiha J, Simonelli F, Bainbridge JW, Michaelides M, van der Spuy J
    DOI: 10.1167/iovs.15-18092

    Biallelic mutations in AIPL1 cause Leber congenital amaurosis (LCA), a devastating retinal degeneration characterized by the loss or severe impairment of vision within the first few years of life. AIPL1 is highly polymorphic with more than 50 mutations and many more polymorphisms of uncertain pathogenicity identified. As such, it can be difficult to assign disease association of AIPL1 variations. In this study, we investigate suspected disease-associated AIPL1 variations, including nonsynonymous missense and intronic variants to validate their pathogenicity.

  • Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease.

    Publication Date: 01/12/2015 on Human molecular genetics
    by Trapani I, Toriello E, de Simone S, Colella P, Iodice C, Polishchuk EV, Sommella A, Colecchi L, Rossi S, Simonelli F, Giunti M, Bacci ML, Polishchuk RS, Auricchio A
    DOI: 10.1093/hmg/ddv386

    Stargardt disease (STGD1) due to mutations in the large ABCA4 gene is the most common inherited macular degeneration in humans. We have shown that dual adeno-associated viral (AAV) vectors effectively transfer ABCA4 to the retina of Abca4-/- mice. However, they express both lower levels of transgene compared with a single AAV and truncated proteins. To increase productive dual AAV concatemerization, which would overcome these limitations, we have explored the use of either various regions of homology or heterologous inverted terminal repeats (ITR). In addition, we tested the ability of various degradation signals to decrease the expression of truncated proteins. We found the highest levels of transgene expression using regions of homology based on either alkaline phosphatase or the F1 phage (AK). The use of heterologous ITR does not decrease the levels of truncated proteins relative to full-length ABCA4 and impairs AAV vector production. Conversely, the inclusion of the CL1 degradation signal results in the selective degradation of truncated proteins from the 5'-half without affecting full-length protein production. Therefore, we developed dual AAV hybrid ABCA4 vectors including homologous ITR2, the photoreceptor-specific G protein-coupled receptor kinase 1 promoter, the AK region of homology and the CL1 degradation signal. We show that upon subretinal administration these vectors are both safe in pigs and effective in Abca4-/- mice. Our data support the use of improved dual AAV vectors for gene therapy of STGD1.

  • Cerebral Involvement in Stargardt's Disease: A VBM and TBSS Study.

    Publication Date: 01/11/2015 on Investigative ophthalmology & visual science
    by Olivo G, Melillo P, Cocozza S, D'Alterio FM, Prinster A, Testa F, Brunetti A, Simonelli F, Quarantelli M
    DOI: 10.1167/iovs.15-16899

    To assess whether and to what extent macro- and/or microstructural modifications are present in the brain of patients with selective central visual loss due to a juvenile macular degeneration, Stargardt's disease (STGD), taking advantage of the complementary information provided by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

  • Ocriplasmin use in a selected case with preserved visual acuity.

    Publication Date: 29/10/2015 on BMC ophthalmology
    by Rossi S, Orrico A, Melillo P, Testa F, Simonelli F, Della Corte M
    DOI: 10.1186/s12886-015-0141-9

    Previous studies described cases of Ocriplasmin injections in patients with vitreo-macular traction and reduced central visual acuity. We describe the first case of a patient with 20/20 visual acuity and vitreo-macular traction treated with Ocriplasmin, and, for the first time in literature, we evaluated the functional changes of the macula in response to pharmacological treatment through multifocal-electroretinogram.

  • Gene therapy of inherited retinal degenerations: prospects and challenges.

    Publication Date: 01/04/2015 on Human gene therapy
    by Trapani I, Banfi S, Simonelli F, Surace EM, Auricchio A
    DOI: 10.1089/hum.2015.030

    Because of its favorable anatomical and immunological characteristics, the eye has been at the forefront of translational gene therapy. Dozens of promising proofs of concept have been obtained in animal models of inherited retinal degenerations (IRDs), and some of them have been relayed to the clinic. The results from the first clinical trials for a congenital form of blindness have generated great interest and have demonstrated the safety and efficacy of intraocular administrations of viral vectors in humans. However, this progress has also generated new questions and posed challenges that need to be addressed to further expand the applicability of gene therapy in the eye, including safe delivery of viral vectors to the outer retina, treatment of dominant IRDs as well as of IRDs caused by mutations in large genes, and, finally, selection of the appropriate IRDs and patients to maximize the efficacy of gene transfer. This review summarizes the strategies that are currently being exploited to overcome these challenges and drive the clinical development of retinal gene therapy.

  • Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy.

    Publication Date: 01/04/2015 on Ophthalmology
    by Aboshiha J, Dubis AM, van der Spuy J, Nishiguchi KM, Cheeseman EW, Ayuso C, Ehrenberg M, Simonelli F, Bainbridge JW, Michaelides M
    DOI: 10.1016/j.ophtha.2014.11.019
  • Standard versus trans-epithelial collagen cross-linking in keratoconus patients suitable for standard collagen cross-linking.

    Publication Date: 18/03/2015 on Clinical ophthalmology (Auckland, N.Z.)
    by Rossi S, Orrico A, Santamaria C, Romano V, De Rosa L, Simonelli F, De Rosa G
    DOI: 10.2147/OPTH.S73991

    Evaluating the clinical results of trans-epithelial collagen cross-linking (CXL) and standard CXL in patients with progressive keratoconus.

  • A pilot study for development of a novel tool for clinical decision making to identify fallers among ophthalmic patients.

    Publication Date: 01/01/2015 on BMC medical informatics and decision making
    by Melillo P, Orrico A, Attanasio M, Rossi S, Pecchia L, Chirico F, Testa F, Simonelli F
    DOI: 10.1186/1472-6947-15-S3-S6

    Falls in the elderly is a major problem. Although falls have a multifactorial etiology, a commonly cited cause of falls in older people is poor vision. This study proposes a method to discriminate fallers and non-fallers among ophthalmic patients, based on data-mining algorithms applied to health and socio-demographic information.