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

  • Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats.

    Publication Date: 01/01/2015 on Mediators of inflammation
    by Rossi S, Di Filippo C, Gesualdo C, Testa F, Trotta MC, Maisto R, Ferraro B, Ferraraccio F, Accardo M, Simonelli F, D'Amico M
    DOI: 10.1155/2015/126408

    Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10-100-1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2, N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

  • Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.

    Publication Date: 01/01/2015 on Mediators of inflammation
    by Rossi S, Di Filippo C, Gesualdo C, Potenza N, Russo A, Trotta MC, Zippo MV, Maisto R, Ferraraccio F, Simonelli F, D'Amico M
    DOI: 10.1155/2015/149381

    This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 μL volume containing 10-100-1000 ng/kg RvD1 1 h post-LPS injection (200 μg, Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-α and NF-κB were reduced.

  • Photorefractive keratectomy on purely refractive accommodative esotropia.

    Publication Date: 01/01/2015 on Seminars in ophthalmology
    by Rossi S, Testa F, Santamaria C, Orrico A, Attanasio M, Simonelli F, De Rosa G
    DOI: 10.3109/08820538.2013.810286

    Results on refractive keratectomy of the treatment of young patients with purely refractive accommodative esotropia.

  • Analysis of the ABCA4 genomic locus in Stargardt disease.

    Publication Date: 20/12/2014 on Human molecular genetics
    by Zernant J, Xie YA, Ayuso C, Riveiro-Alvarez R, Lopez-Martinez MA, Simonelli F, Testa F, Gorin MB, Strom SP, Bertelsen M, Rosenberg T, Boone PM, Yuan B, Ayyagari R, Nagy PL, Tsang SH, Gouras P, Collison FT, Lupski JR, Fishman GA, Allikmets R
    DOI: 10.1093/hmg/ddu396

    Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of ABCA4 in STGD patients identifies compound heterozygous or homozygous disease-associated alleles in 65-70% of patients and only one mutation in 15-20% of patients. This study was designed to find the missing disease-causing ABCA4 variation by a combination of next-generation sequencing (NGS), array-Comparative Genome Hybridization (aCGH) screening, familial segregation and in silico analyses. The entire 140 kb ABCA4 genomic locus was sequenced in 114 STGD patients with one known ABCA4 exonic mutation revealing, on average, 200 intronic variants per sample. Filtering of these data resulted in 141 candidates for new mutations. Two variants were detected in four samples, two in three samples, and 20 variants in two samples, the remaining 117 new variants were detected only once. Multimodal analysis suggested 12 new likely pathogenic intronic ABCA4 variants, some of which were specific to (isolated) ethnic groups. No copy number variation (large deletions and insertions) was detected in any patient suggesting that it is a very rare event in the ABCA4 locus. Many variants were excluded since they were not conserved in non-human primates, were frequent in African populations and, therefore, represented ancestral, and not disease-associated, variants. The sequence variability in the ABCA4 locus is extensive and the non-coding sequences do not harbor frequent mutations in STGD patients of European-American descent. Defining disease-associated alleles in the ABCA4 locus requires exceptionally well characterized large cohorts and extensive analyses by a combination of various approaches.

  • Macular function and morphologic features in juvenile stargardt disease: longitudinal study.

    Publication Date: 01/12/2014 on Ophthalmology
    by Testa F, Melillo P, Di Iorio V, Orrico A, Attanasio M, Rossi S, Simonelli F
    DOI: 10.1016/j.ophtha.2014.06.032

    To evaluate disease progression in a cohort of patients with a clinical and genetic diagnosis of Stargardt disease.

  • A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2.

    Publication Date: 24/07/2014 on BMC medical genetics
    by Mozzillo E, Delvecchio M, Carella M, Grandone E, Palumbo P, Salina A, Aloi C, Buono P, Izzo A, D'Annunzio G, Vecchione G, Orrico A, Genesio R, Simonelli F, Franzese A
    DOI: 10.1186/1471-2350-15-88

    Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2.

  • Macular abnormalities in Italian patients with retinitis pigmentosa.

    Publication Date: 01/07/2014 on The British journal of ophthalmology
    by Testa F, Rossi S, Colucci R, Gallo B, Di Iorio V, della Corte M, Azzolini C, Melillo P, Simonelli F
    DOI: 10.1136/bjophthalmol-2013-304082

    To investigate the prevalence of macular abnormalities in a large Caucasian cohort of patients affected by retinitis pigmentosa (RP).

  • Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors.

    Publication Date: 01/04/2014 on Gene therapy
    by Colella P, Trapani I, Cesi G, Sommella A, Manfredi A, Puppo A, Iodice C, Rossi S, Simonelli F, Giunti M, Bacci ML, Auricchio A
    DOI: 10.1038/gt.2014.8

    Gene therapy with adeno-associated viral (AAV) vectors is limited by AAV cargo capacity that prevents their application to the inherited retinal diseases (IRDs), such as Stargardt disease (STGD) or Usher syndrome type IB (USH1B), which are due to mutations in genes larger than 5 kb. Trans-splicing or hybrid dual AAV vectors have been successfully exploited to reconstitute large gene expression in the mouse retina. Here, we tested them in the large cone-enriched pig retina that closely mimics the human retina. We found that dual AAV trans-splicing and hybrid vectors transduce pig photoreceptors, the major cell targets for treatment of IRDs, to levels that were about two- to threefold lower than those obtained with a single AAV vector of normal size. This efficiency is significantly higher than that in mice, and is potentially due to the high levels of dual AAV co-transduction we observe in pigs. We also show that subretinal delivery in pigs of dual AAV trans-splicing and hybrid vectors successfully reconstitute, albeit at variable levels, the expression of the large genes ABCA4 and MYO7A mutated in STGD and USH1B, respectively. Our data support the potential of dual AAV vectors for large gene reconstitution in the cone-enriched pig retina that is a relevant preclinical model.

  • Inhibition of ocular aldose reductase by a new benzofuroxane derivative ameliorates rat endotoxic uveitis.

    Publication Date: 01/01/2014 on Mediators of inflammation
    by Di Filippo C, Zippo MV, Maisto R, Trotta MC, Siniscalco D, Ferraro B, Ferraraccio F, La Motta C, Sartini S, Cosconati S, Novellino E, Gesualdo C, Simonelli F, Rossi S, D'Amico M
    DOI: 10.1155/2014/857958

    The study investigated the effects of the aldose reductase (AR) inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane (herein referred to as BF-5m) on the biochemical and tissue alterations induced by endotoxic uveitis in rats. BF-5m has been administered directly into the vitreous, in order to assess the expression and levels of (i) inflammatory markers such as the ocular ubiquitin-proteasome system, NF-κB, TNF-α, and MCP-1; (ii) prooxidant and antioxidant markers such as nitrotyrosine, manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX); (iii) apoptotic/antiapoptotic factors caspases and Bcl-xl; (iv) markers of endothelial progenitor cells (EPCs) recruitment such as CD34 and CD117. 5 μL of BF-5m (0.01; 0.05; and 0.1 μM) into the right eye decreased in a dose-dependent manner the LPS-induced inflammation of the eye, reporting a clinical score 1. It reduced the ocular levels of ubiquitin, 20S and 26S proteasome subunits, NF-κB subunits, TNF-α, MCP-1, and nitrotyrosine. BF-5m ameliorated LPS-induced decrease in levels of MnSOD and GPX. Antiapoptotic effects were seen from BF-5m by monitoring the expression of Bcl-xl, an antiapoptotic protein. Similarly, BF-5m increased recruitment of the EPCs within the eye, as evidenced by CD34 and CD117 antibodies.

  • Vitreous substitutes: the present and the future.

    Publication Date: 01/01/2014 on BioMed research international
    by Donati S, Caprani SM, Airaghi G, Vinciguerra R, Bartalena L, Testa F, Mariotti C, Porta G, Simonelli F, Azzolini C
    DOI: 10.1155/2014/351804

    Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties.