Project 04

Study of microRNA expression profile in Central Areolar Choroidal Dystrophy. Translational study using a new CRISPR-generated animal model.

Host institution: Universidad de Alicante
PhD: Yes
Duration: 36

Central Areolar Choroidal Dystrophy (CACD) is a monogenic hereditary retinal dystrophy that involves a progressive retinal degeneration.


It usually causes a gradual loss of visual acuity between 30 and 60 years old, and color perception impairments. In most cases, CACD presents an autosomal dominant inheritance pattern in which patients carry a single mutation in the peripherin gene (PRPH2 or RDS, Retinal Degeneration Slow), although other genes may be involved in some individuals.

Peripherin is a glycoprotein essential for generating and maintaining the photoreceptor outer segment disks where retinal phototransduction takes place. Five different mutations in peripherin have been histologically and functionally described as causing this disease and this project will focus on the p.Arg195Leu mutation which was firstly described in a carrier family in Japan and later in German and Spanish families. In Spain, CACD has been diagnosed in a large family from the Iguña Valley, Cantabria. The existence of this family, with a large number of members affected with the same mutation, is a unique opportunity to in-depth study the CACD pathology in a homogeneous population.

Thus, our new CRISPR-generated animal model (Prph2 KI/WT mouse), that reproduces the same pathological characteristics than CACD patients, will allow a better description of the disease and increase the current knowledge about it. The main aim of this project is to study for the first time the total microRNA expression profile in the retina of Prph2 KI/WT mouse and particularly focusing on the miRNAs which have an important role in the maintenance and function of photoreceptor outer segments (e.g miR-183/96/182 cluster) and also on those miRNAs associated with inflammatory pathways (e.g. miR-155 and miR-124). In addition, a study of retinal morphology and physiology will be carried out to describe the neuropathological events that occur in CACD patients and in this new mouse model carrying the same mutation. This study will allow to test new neuroprotective therapies using RNA-based strategies in Prph2 KI/WT mice, as a first approach for translational medicine.


Expected results

  1. Analysis of retinal morphology and physiology to describe the neuropathological events that occur in CACD patients and in this new mouse model carrying the same mutation
  2. Assessment the global expression profile of mRNAs and miRNAs in Prph2 KI/WT mouse across the progression of the retinal neurodegenerative process. To establish a correlation between the miR-183/96/182 cluster and their relationship with peripherin mutation
  3. In silico identification of key pathways regulated by the RNAs and miRNAs that are modified by the peripherin mutation and specifically miR-155 and miR-124
  4. Evaluation of a possible therapy for CACD using RNA-based strategies in Prph2 KI/WT mouse

Planned secondments

  1. B8, supervisor: Sandro Banfi
    Purpose: Training in sequencing RNA
  2. AP7, supervisor: Beatriz Llamusí
    Purpose: business training
  3. B7, supervisor: Aileen Murphy
    Purpose: economic training