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

  • Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study.

    Publication Date: 02/07/2019 on Documenta ophthalmologica. Advances in ophthalmology
    by Stingl K, Kurtenbach A, Hahn G, Kernstock C, Hipp S, Zobor D, Kohl S, Bonnet C, Mohand-Saïd S, Audo I, Fakin A, Hawlina M, Testa F, Simonelli F, Petit C, Sahel JA, Zrenner E
    DOI: 10.1007/s10633-019-09704-8

    Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH).

  • Early posterior vitreous detachment is associated with LAMA5 dominant mutation.

    Publication Date: 27/12/2018 on Ophthalmic genetics
    by Napolitano F, Di Iorio V, Di Iorio G, Melone MAB, Gianfrancesco F, Simonelli F, Esposito T, Testa F, Sampaolo S
    DOI: 10.1080/13816810.2018.1558261

    Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.

  • Usher syndrome and color vision.

    Publication Date: 17/07/2018 on Current eye research
    by Kurtenbach A, Hahn G, Kernstock C, Hipp S, Zobor D, Stingl K, Kohl S, Bonnet C, Mohand-Saïd S, Sliesoraityte I, Sahel JA, Audo I, Fakin A, Hawlina M, Testa F, Simonelli F, Petit C, Zrenner E
    DOI: 10.1080/02713683.2018.1501804

    Purpose The aim of this study is to report on the results of color vision testing in a European cohort of patients with Usher syndrome (USH). We describe the results in relation to Usher type (USH1, USH2), age and visual acuity. Methods and Methods The color vision of 220 genetically confirmed adult USH patients, aged 18-70 years, was analyzed with one of 3 methods: the Farnsworth D-15 Dichotomous test (D-15) along with the Lanthony desaturated 15 Hue tests (D-15d), the Roth 28-Hue test, or the Ishihara 14-plate test. Visual acuity was measured with either the ETDRS or the SNELLEN charts. The Confusion index, the Selectivity index and the Confusion angle were calculated for the panel tests and used for analysis. The number of plates that could not be read were analyzed for the Ishihara test. Results For the panel tests, the degree of color loss (Confusion index) is similar in both subtypes of USH, but the polarization of error scores (Selectivity index) is significantly lower in USH1 than USH2, showing more diffuse errors than those found in USH2. There is no significant correlation between logMAR visual acuity and the Confusion or the Selectivity indices. Additionally, we find a significant correlation between patient age and the degree and the polarity of the loss only in USH2. There was no difference between USH1 and USH2 in the results of the Ishihara test. Conclusions The examination of color vision in patients with USH, shows a significant difference in the pattern of color vision loss in USH1 and USH2 patients, but not in the severity of the loss. In USH2 we find a correlation between patient age and the degree and the polarity of the loss. These results may be due to differences in the pathogenesis of retinal dystrophy in USH1 and USH2.

  • ASSOCIATION BETWEEN GENOTYPE AND DISEASE PROGRESSION IN ITALIAN STARGARDT PATIENTS: A Retrospective Natural History Study.

    Publication Date: 10/04/2018 on Retina (Philadelphia, Pa.)
    by Di Iorio V, Orrico A, Esposito G, Melillo P, Rossi S, Sbordone S, Auricchio A, Testa F, Simonelli F
    DOI: 10.1097/IAE.0000000000002151

    To investigate the natural history of Stargardt disease over a multiyear follow-up.

  • Visual Cortex Activation in Patients With Stargardt Disease.

    Publication Date: 01/03/2018 on Investigative ophthalmology & visual science
    by Melillo P, Prinster A, Di Iorio V, Olivo G, D'Alterio FM, Cocozza S, Orrico A, Quarantelli M, Testa F, Brunetti A, Simonelli F
    DOI: 10.1167/iovs.17-22900

    Primary visual cortex (PVC) contains a retinotopic map in which the central visual field (CVF) is highly magnified compared to the peripheral field. Several studies have used functional magnetic resonance imaging (fMRI) in patients with macular degeneration to assess the reorganization of visual processing in relationship with the development of extrafoveal preferred retinal locus (PRL). We evaluated the functional response in PVC and its correlation with retinal parameters in patients with Stargardt disease due to ABCA4 mutations (STGD1).

  • The renal lesions in Bardet-Biedl Syndrome: history before and after the discovery of BBS genes.

    Publication Date: 01/02/2018 on Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia
    by Viggiano D, Zacchia M, Simonelli F, Di Iorio V, Anastasio P, Capasso G, De Santo NG
  • Autosomal dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation.

    Publication Date: 24/01/2018 on Clinical genetics
    by Napolitano F, Di Iorio V, Testa F, Tirozzi A, Reccia MG, Lombardi L, Farina O, Simonelli F, Gianfrancesco F, Di Iorio G, Melone MAB, Esposito T, Sampaolo S
    DOI: 10.1111/cge.13217

    We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A>G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.

  • Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15.

    Publication Date: 21/12/2017 on JCI insight
    by Botta S, de Prisco N, Marrocco E, Renda M, Sofia M, Curion F, Bacci ML, Ventrella D, Wilson C, Gesualdo C, Rossi S, Simonelli F, Surace EM
    DOI: 10.1172/jci.insight.96560

    The genome-wide activity of transcription factors (TFs) on multiple regulatory elements precludes their use as gene-specific regulators. Here we show that ectopic expression of a TF in a cell-specific context can be used to silence the expression of a specific gene as a therapeutic approach to regulate gene expression in human disease. We selected the TF Krüppel-like factor 15 (KLF15) based on its putative ability to recognize a specific DNA sequence motif present in the rhodopsin (RHO) promoter and its lack of expression in terminally differentiated rod photoreceptors (the RHO-expressing cells). Adeno-associated virus (AAV) vector-mediated ectopic expression of KLF15 in rod photoreceptors of pigs enables Rho silencing with limited genome-wide transcriptional perturbations. Suppression of a RHO mutant allele by KLF15 corrects the phenotype of a mouse model of retinitis pigmentosa with no observed toxicity. Cell-specific-context conditioning of TF activity may prove a novel mode for somatic gene-targeted manipulation.

  • Triple Vectors Expand AAV Transfer Capacity in the Retina.

    Publication Date: 05/12/2017 on Molecular therapy : the journal of the American Society of Gene Therapy
    by Maddalena A, Tornabene P, Tiberi P, Minopoli R, Manfredi A, Mutarelli M, Rossi S, Simonelli F, Naggert JK, Cacchiarelli D, Auricchio A
    DOI: 10.1016/j.ymthe.2017.11.019

    Retinal gene transfer with adeno-associated viral (AAV) vectors holds great promise for the treatment of inherited retinal degenerations (IRDs). One limit of AAV is its transfer capacity of about 5 kb, which can be expanded to about 9 kb, using dual AAV vectors. This strategy would still not suffice for treatment of IRDs such as Usher syndrome type 1D or Alström syndrome type I (ALMS) due to mutations in CDH23 or ALMS1, respectively. To overcome this limitation, we generated triple AAV vectors, with a maximal transfer capacity of about 14 kb. Transcriptomic analysis following triple AAV transduction showed the expected full-length products along a number of aberrant transcripts. However, only the full-length transcripts are efficiently translated in vivo. We additionally showed that approximately 4% of mouse photoreceptors are transduced by triple AAV vectors and showed correct localization of recombinant ALMS1. The low-photoreceptor transduction levels might justify the modest and transient improvement we observe in the retina of a mouse model of ALMS. However, the levels of transduction mediated by triple AAV vectors in pig retina reached 40% of those observed with single vectors, and this bodes well for further improving the efficiency of triple AAV vectors in the retina.

  • Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques.

    Publication Date: 28/11/2017 on International ophthalmology
    by Rossi S, Santamaria C, Boccia R, De Rosa L, D'Alterio FM, Simonelli F, De Rosa G
    DOI: 10.1007/s10792-017-0772-3

    To evaluate the clinical results of standard, transepithelial (TE) and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive keratoconus.