Grimm Lab for Retinal Cell Biology, University of Zurich, Switzerland

General Research Area

Although many patients worldwide suffer from inherited retinal degenerations, successful therapies are still highly needed for the treatment of blinding diseases like age related macular degeneration (AMD) or Retinitis Pigmentosa (RP). The diversity of the stimuli (endogenous and exogenous) and the heterogeneity of the phenotypes makes it difficult to design treatments for patients. The main reason for the lack of effective therapies, however, may be the incomplete understanding of the molecular events leading to retinal cell death and hence to the impairment of vision.

Our work focuses on the elucidation of the biochemical events and molecular signaling cascades during retinal degenerations. The goal is to understand the pathways induced by the diverse stimuli in order to develop neuroprotective strategies which may ultimately lead to the rescue of vision in patients.

General Research Questions

Research Aims_1

Why do photoreceptors degenerate?
To understand retinal disease mechanisms and to develop therapeutic strategies, it is mandatory to understand retinal physiology on a systemic and on a molecular level. Endogenous and exogenous stimuli need to be defined which causes the switch from physiology to pathophysiology and thus to retinal degeneration.

How is cell death induced and executed?
Having defined the stimuli inducing retinal degeneration, the investigation of the molecular responses and signaling cascades is of essential importance not only to identify the mechanisms of cell death execution but especially also to learn about endogenous rescue mechanisms activated to protect visual cells.

How are dead cells cleared?
Degeneration of retinal cells generates cellular debris which needs to be removed from the retina to avoid further damage. Phagocytosis is the central process responsible for the clearance process. Cells of the retinal pigment epithelium as well as resident and invading microglias/macrophages are the main phagocytes in the retina. Inflammatory processes may be involved in the recruitment of phagocytic cells. Controlled manipulation of these processes may reduce retinal damage and may be beneficial for diseases like AMD.

How can cell death be inhibited?
Recognition of the above mechanisms is required for the development of efficient strategies to reduce retinal degeneration and to prolong the period of useful vision for patients. Such strategies may be based on the controlled stimulation of endogenous and thus ‘natural’ rescue mechanism or on the interference with death mechanisms by the application of exogenous compounds. It is our goal to translate the acquired knowledge into clinical trials and, finally, into clinical applications.

The Lab of Retinal Cell Biology belongs to the Dept. of Ophthalmology, University Eye Hospital Zurich.
Head of Department: Prof. Dr. Klara Landau