Ophthalmogenetics

Research group leader

Staff

  • Bulla Emanuele, PhD Student
  • Steiner Beatrice, PhD Student

Research focuses

  • Inherited retinal diseases
  • Retinal nuclear receptors
  • Retinal development
  • Photoreceptor differentiation

Methods

  • Molecular and cellular biology: structural and functional analyses of ligand-activated transcription factors in vitro and in cell culture, cell-specific gene expression, promoter analyses, gene expression profiling, transcriptomics, laser microdissection
  • In vivo analyses: electroretinography (ERG), funduscopy, optical coherence tomography (OCT), angiography
  • Mouse genetics: embryonic stem cells, genetically modified mice
  • Human genetics: next-generation sequencing, genomics, bioinformatics, locus-specific databases

Short description

Current research focuses on inherited retinal diseases, retinal development, photoreceptor-specific gene transcription and nuclear receptor-related ocular pathologies.

Recessive mutations in the photoreceptor-specific nuclear receptor NR2E3 cause enhanced S-cone sensitivity syndrome (ESCS) also called Goldmann-Favre syndrome. In presence of these defective NR2E3 proteins or in the absence of NR2E3, there is a misspecification of dim light-sensitive rod versus bright-light sensitive cone photoreceptors. Patients show a pathognomonic increase in sensitivity to blue light and are night blind. In contrast, a unique dominant NR2E3 mutation (p.G56R) causes retinitis pigmentosa (RP), i.e. a rod-cone dystrophy leading eventually to visual impairment and blindness. To understand the molecular mechanisms underlying the high variability in clinical phenotypes observed in recessive and dominant NR2E3-linked retinal degenerations, we perform structural and functional analyses in vitro, in cellular models and in vivo in mouse models.

We also aim at elucidating in genetically modified mice whether peroxisome proliferator-activated receptors (PPARs) have a pro- or anti-angiogenic action during choroidal neovascularization. This fundamental study contributes to the evaluation of synthetic PPAR ligands as therapeutic agents for ‘wet’ (exudative) age-related macular degeneration and diabetic microvascular damage.