Ueffing Lab

Molecular Biology of Retinal Degenerations

Home » Labs » Ueffing Lab » Research Topics » Retinal degeneration and therapy development

Retinal degeneration and therapy development

Dying photorectors marked in green. (© Arango-Gonzalez)

Inherited forms of RD affect the light-sensing photoreceptors leading to an irreversible vision loss. Different forms of RD present with substantial clinical and genetic heterogeneity; nevertheless, common features of all forms are (1) degeneration of photoreceptors, subsequently leading to blindness, and (2) no available treatment. Taking a systems biology approach combining bioanalytic, proteogenomic and computational analytical strategies, we aim at in-depth understanding of overarching rod and cone cell death pathways affected in RD. Based on a holistic understanding of key systemic perturbations that cause disease, we are currently developing therapy for RD that is mutation independent.

In particular, our research group has provided a proof of concept that rebalancing defects in proteostasis and energy consumption can significantly slow down RD. Especially in photoreceptors (PR), the production of large quantities of visual pigment generates a huge demand for energy equivalents and protein folding capacity. Maintenance of protein and energy homeostasis comes to the limit, when a cell gets out of balance due to disease. Importantly, this happens independently of the disease-associated mutation. Similarly, our therapeutic principle is mutation independent.

Current Projects:

  • Proteostasis modulators as a mutation-independent treatment for retinal degeneration: Pro-Cure – Tistou & Charlotte Kerstan Stiftung (2023 – 2024)
  • Auswirkungen der VCP-Hemmung auf die Netzhautdegeneration – Maloch Stiftung (2022 – 2024)
  • Keeping protein homeostasis in cone photoreceptors: effect of VCP inhibition on primary and secondary cone degeneration. Pro Retina - Stiftung zur Verhütung von Blindheit (2021-2023)
  • Targeting Proteostasis in the RhoI256del Model of Retinitis Pigmentosa: Rho-Cure – Tistou & Charlotte Kerstan Stiftung (2022 – 2023)
  • Development of pharmacological treatment options to halt retinal degeneration caused by dominant rhodopsin mutations. Rho-Cure – Tistou & Charlotte Kerstan Stiftung (2018 – 2023)
  • Targeting Proteostasis and Protein Quality Control in Photoreceptors Towards Therapeutic Intervention. Foundation Fighting Blindness (FFB), Program Project Award (2018-2022) https://www.photoreceptorproteostasis.org/


  • Scott Harris, Cleave Therapeutics, Inc. San Francisco, California, US.
  • Michael Cheetham, Institute of Ophthalmology, Faculty of Brain Sciences, University College London, London, UK. 
  • Paolo Caliceti, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova - Italy
  • Stefano Salmaso, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova - Italy
  • Olivier Zelphati, OZ Biosciences SAS, Marseille, France.
  • Ronald Roepman, Department of Human Genetics, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
  • Uwe Wolfrum, Institut fuer Zoologie, Johannes-Gutenberg Universitaet Mainz, Mainz, Germany.
  • Arto Urtti, Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland , Kuopio, Finland.
  • Tsui-Fen Chou, Biology and Biological Engineering, Caltech - California Institute of Technology,  Pasadena, California, USA.
  • Raymond J. Deshaies, AMGEN, Inc. Thousand Oaks, California, US.

Selected Publications

1.         Sen, M., O. Kutsyr, B. Cao, S. Bolz, B. Arango-Gonzalez, and M. Ueffing. "Pharmacological Inhibition of the Vcp/Proteasome Axis Rescues Photoreceptor Degeneration in Rho(P23h) Rat Retinal Explants." Biomolecules 11, no. 10 (2021).

2.         Griciuc, A., L. Aron, M. J. Roux, R. Klein, A. Giangrande, and M. Ueffing. "Inactivation of Vcp/Ter94 Suppresses Retinal Pathology Caused by Misfolded Rhodopsin in Drosophila." PLoS Genet 6, no. 8 (2010).

3.         Cao, Bowen, Merve Sen, Tina Beyer, Tobias Leonhard, Sally Williamson, Ana Cristina Almansa Garcia, Sylvia Bolz, Blanca Arango Gonzalez, and Marius Ueffing. "The Degradation of Mutant Rhodopsinile256del Follows the Vcp-Dependent Endoplasmic-Reticulum-Associated Protein Degradation pathway." Acta Ophthalmol 100, no. S267 (2022).

4.         Arango-Gonzalez, Blanca, Merve Sen, Rosellina Guarascio, Kalliopi Ziaka, Eva M. del Amo, Kwan Hau, Hannah Poultney, Rowan Asfahani, Arto Urtti, Tsui-Fen Chou, Sylvia Bolz, Raymond J. Deshaies, Wadood Haq, Michael E. Cheetham, and Marius Ueffing. "Inhibition of Vcp Preserves Retinal Structure and Function in Autosomal Dominant Retinal Degeneration." bioRxiv (2020): 2020.11.17.384669.

5.         Sen, M., M. Al-Amin, E. Kicková, A. Sadeghi, J. Puranen, A. Urtti, P. Caliceti, S. Salmaso, B. Arango-Gonzalez, and M. Ueffing. "Retinal Neuroprotection by Controlled Release of a Vcp Inhibitor from Self-Assembled Nanoparticles." J Control Release 339 (2021): 307-20.

6.         Sen, M., M. Bassetto, F. Poulhes, O. Zelphati, M. Ueffing, and B. Arango-Gonzalez. "Efficient Ocular Delivery of Vcp Sirna Via Reverse Magnetofection in Rho P23h Rodent Retina Explants." Pharmaceutics 13, no. 2 (2021).

7.         Almansa García, Ana Cristina, Bowen Cao, Merve Sen, Sylvia Bolz, Blanca Arango-Gonzalez, and Marius Ueffing. "Effect of Protein Homeostasis Modulation in Primary Cone Degeneration." Acta Ophthalmol 100, no. S267 (2022).

8.         Griciuc, A., L. Aron, and M. Ueffing. "Er Stress in Retinal Degeneration: A Target for Rational Therapy?" Trends Mol Med 17, no. 8 (2011): 442-51.

9.         Griciuc, A., M. J. Roux, J. Merl, A. Giangrande, S. M. Hauck, L. Aron, and M. Ueffing. "Proteomic Survey Reveals Altered Energetic Patterns and Metabolic Failure Prior to Retinal Degeneration." J Neurosci 34, no. 8 (2014): 2797-812.

10.       Tolone, A., M. Sen, Y. Chen, M. Ueffing, B. Arango-Gonzalez, and F. Paquet-Durand. "Pathomechanisms of Inherited Retinal Degeneration and Perspectives for Neuroprotection." Cold Spring Harb Perspect Med (2022).

11.       Al-Amin, M. D., F. Mastrotto, A. Subrizi, M. Sen, T. Turunen, B. Arango-Gonzalez, M. Ueffing, A. Malfanti, A. Urtti, S. Salmaso, and P. Caliceti. "Tailoring Surface Properties of Liposomes for Dexamethasone Intraocular Administration." J Control Release 354 (2023): 323-36.

12.       Kickova, E., A. Sadeghi, J. Puranen, S. Tavakoli, M. Sen, V. P. Ranta, B. Arango-Gonzalez, S. Bolz, M. Ueffing, S. Salmaso, P. Caliceti, E. Toropainen, M. Ruponen, and A. Urtti. "Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery." Pharmaceutics 14, no. 1 (2021).

13.       Bassetto, M., M. Sen, F. Poulhes, B. Arango-Gonzalez, E. Bonvin, C. Sapet, M. Ueffing, and O. Zelphati. "New Method for Efficient Sirna Delivery in Retina Explants: Reverse Magnetofection." Bioconjug Chem 32, no. 6 (2021): 1078-93.