PhD Project Pathogenic changes in retinal dystrophy

Project description 

Retinal dystrophies are a group of degenerative disorders of the retina; the light-sensitive layer in the back of the eye. Inherited retinal dystrophies such as Retinitis Pigmentosa is one of the most common blinding diseases affecting about 1 in 4,000 people. The disease manifests with progressive loss of photoreceptor cells, whereas the morphology of the other retinal layers appear more or less intact. More than 80 genes have been implicated and in only 20-30% of all autosomal recessive inherited cases the pathogenic variant is detected. The gene products of the known disease genes are involved in vital processes in different layers of the retina, including the visual cycle and the phototransduction cascade. Even though we know how the underlying pathogenic variant interferes with normal retinal function, the precise mechanisms leading to photoreceptor death, when one of the processes is defective, are not well understood.

We and others have shown that the receptor megalin is involved in eye size determination and that deficiency causes retinal dystrophy. This is in line with the phenotype of patients with pathological variants in the megalin encoding gene (Donnai-Barrow syndrome) suffering from high myopia. Megalin is expressed in the retinal pigment epithelium (RPE), which oversees the continuous supply of 11-cis-retinal to the photoreceptors, which is re-generated in the visual cycle from all-trans retinal produced in the phototransduction cascade in photoreceptors or from blood derived all-trans-retinol. Our new data indicates that the conversion of retinyl ester to 11-cis-retinol in the visual cycle is delayed in megalin knockout mice. The conversion of retinyl palmitate to 11-cis-retinol is performed by the retinol isomerohydrolase (RPE65). Thus, megalin deletion might interfere with the visual cycle at the RPE65 step, which is compatible with megalin being localised to vesicles/microsomal membranes in the RPE where the visual cycle occurs, and the pathogenesis might be shared with Retinitis Pigmentosa caused by RPE65 gene mutations.

The PhD project aims to investigate the role of megalin in the eye by using molecular techniques, mouse models, eye cup explants and high resolution microscopy. To determine the pathogenic changes in the retina in the megalin-induced retinopathy and in the RPE65 model spatial transcriptomics will be applied


We are looking for a highly motivated, dedicated, and ambitious candidate with:

  • A Master’s degree in Molecular Medicine, Molecular Biology, Biology, Biomedicine, Medicine or equivalent.
  • A strong interest in ocular physiology and bioinformatic analyses (RNA seq, use of R).
  • Solid experience with basic methods for molecular biology, biochemistry and cell biology.
  • Experience with animal work (mouse), confocal microscopy, transcriptomics and bioinformatics are advantageous.
  • Commitment and drive for performing academic research.
  • An analytical mindset for developing innovative scientific or technical solutions.
  • Good collaborative and project management skills, a strong sense of responsibility, and an interest in working in an interdisciplinary environment.

We offer:

  • A three-year PhD position in a highly stimulating, supportive, and interdisciplinary research environment.
  • Access to state-of-the-art equipment, facilities, and infrastructure.
  • Research training and supervision on a daily basis.
  • Enrollment in the PhD school of Health, AU.
  • Training in a wide range of skills including research management, communication, presentations, writing of manuscripts, teaching etc.

How to apply

Please submit your application via this link. Application deadline is 16 April 2023 23:59 CET. Preferred starting date is 1 August 2023. 

For information about application requirements and mandatory attachments, please see our application guide 

Further information

Please contact Associate Professor Rikke Nielsen,, for further information.

All interested candidates are encouraged to apply, regardless of their personal background. Salary and terms of employment are in accordance with applicable collective agreement.