Enzmann Lab

Enzmann Lab

Ongoing Projects

Ongoing projects Experimental Ophthalmology

Retinal nuclear receptors (Group Escher)

Nuclear receptors are a large family of ligand-activated transcription factors, acting as molecular switches in development, metabolism, homeostasis etc. Nuclear receptors are essential for proper retinal development, and, for instance, the absence of a functional photoreceptor-specific nuclear receptor NR2E3 causes a misspecification of dim light-sensitive rod versus bright light-sensitive cone photoreceptors (Goldmann-Favre syndrome, enhanced S-cone sensitivity syndrome), or a degeneration of rod photoreceptors (retinitis pigmentosa). In addition to these rare inherited retinal dystrophies, functions of the fatty acid-activated nuclear receptors PPARs (peroxisome proliferator-activated receptors) are evaluated in more frequent retinal diseases such as diabetic retinopathy and age-related macular degeneration. To identify the various disease mechanisms underlying nuclear receptor-linked retinal diseases we resort to structural and functional analyses in vitro, in cellular models and in vivo.

Retinal degeneration / regeneration (Group Enzmann)

Age-related macular degeneration and retinitis pigmentosa are leading causes for vision loss in the industrialized world. So far, no effective treatment to restore the lost vision is available. In order to develop new therapeutical approaches in this regard, we are employing a variety of animal models in zebrafish (ZF) and mouse with induced retinal degeneration. Thereby, pharmacological treatment using cell type-specific toxins (e.g., NaIO3, MNU) and laser-induced damage of the outer nuclear layer are means to induce the pathological changes in the retina. The aim of our experiments is the identification of differences between ZF, a species with high regenerative capacity, and mouse, carrying rather limited regenerative potential, during retinal degeneration and how to modulate them towards regeneration. Thereby, we are investigating the employment of Müller cells, the main macroglia in the retina, as potential candidates for replacing degenerated photoreceptors and/or RPE. Future research will also focus on an active modulation of Müller cell-epithelial transition (MC-ET) as a pivotal process during degeneration/regeneration and the treatment of the chronic gliosis in mice with anti-fibrotic drugs as we found similarities to wound healing (fibrosis).

Retinal Fibrosis (Group Zandi)

Despite advancements in vitreoretinal surgery, proliferative vitreoretinal diseases, such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR), remain common causes of severe vision loss among the working population and its prevention or targeted treatment is of high priority. With our research, we aim to identify specific molecules and signaling cascades that lead to excessive fibrosis in the eye and therefore to irreversible loss if vision. The Rho/ROCK signaling pathway is implicated in various cellular functions, such as cell proliferation, adhesion, migration, and contraction. Therefore, one specific aim is to study the involvement of the Rho/ROCK signaling pathway in the pathogenesis of vitreoretinal diseases. In addition to candidate drug molecules, such as ROCK isoforms or other molecules from the Rho/ROCK signaling pathway, optimal therapeutic drug delivery systems for vitreoretinal diseases will be established.

Ocular Immunology (Group Zinkernagel)

Inflammation has been associated with the development and progression of severe retinal diseases, such as age-related macular degeneration (AMD) and retinal vein occlusion (RVO), characterized by impaired vision and even blindness. Thus, it is of great importance to establish new pharmacological targets for the treatment of retinal disease to prevent vision loss and to improve the quality of life for affected people. The major research interests of our group focus on investigating the role of innate immune cells in retinal disease, with emphasis in resident microglia and infiltrating myeloid-derived cells as well as other inflammatory components such as cytokines and chemokines. Experimental mouse models of choroidal neovascularization, retinal vein occlusion and lipopolysaccharide (LPS)-induced retinal inflammation are employed, together with genetically modified animals, in vivo imaging techniques and molecular and cellular approaches. The goal of our research is to gain a better understanding on the role of innate immune cells in retinal disease progression and to investigate potential therapeutic targets.

Microbiome (Group Zysset)

The human microbiome is composed of trillions of bacteria, viruses and fungi living in and on the human body. In 2007, the Human Microbiome Project characterized the microbiomes at five different body sites including the skin, gastrointestinal tract, oral cavity, nasal passages and urogenital tract in healthy human subjects, thereby improving the understanding of the microbial flora involved in human health and disease. Under normal physiological conditions, the microbiome is a homeostatic ecosystem with several essential functions. However, disruption of this homeostasis, called dysbiosis, is associated with multiple diseases. Our intestinal microbiome project investigates associations of the gut microbiome with several eye diseases such as age-related macular degeneration and retinal artery occlusion. We are using whole-metagenome shotgun sequencing to characterize the intestinal microbiome of human subjects. Our state-of-the-art bioinformatics pipeline allows dissecting compositional and associated functional profiles of the microbes in the gut. Furthermore, there are several known niches of the human microbiome including the skin or the oral cavity. Surprisingly, there is also a little known niche of the microbiome on the ocular surface. Its microbial composition, called the ocular surface microbiome, remains limited and still needs more investigation. We are disentangling the interplay between the microbial composition on the ocular surface and proteins in tear fluid and potential impacts on ocular health and disease. These projects are performed in human subjects, but we are also employing animal models.