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Project

Peroxisomes and vision: what is the role of peroxisomal 􀉴􀍲oxidation in the retina?

The crucial function of peroxisomes for vision is illustrated by the fact that prominent ophthalmological pathology, including retinopathy, occurs in nearly all peroxisomal diseases. Peroxisomes are subcellular organelles that play an essential role in oxygen and lipid metabolism, but their precise contribution to the maintenance of tissue homeostasis is still largely obscure. According to our preliminary data, the retina of mice with peroxisomal β-oxidation dysfunction  (Mfp2 knockout) deteriorates within a few months. In this project, we will investigate the mechanisms underlying this degeneration. We hypothesize that peroxisomal β-oxidation is essential both in photoreceptors and in the retinal pigment epithelium (RPE) to maintain retinal intergrity. Besides systemic Mfp2-/- mice, also a conditional mouse model with selective inactivation of MFP2 in the RPE will be used. In addition, human MFP2-deficient RPE cells will be generated from embryonic pluripotent stem cells. Dysfunction of cellular processes such as lipid metabolism, redox balance and (auto)phagocytic capacity will be investigated. We will also perform preclinical studies to restore MFP2 function by viral delivery. To accomplish these goals, we will use cutting edge approaches and start up collaborations with leaders in diverse fields. This investigation will increase our basic understanding of the role of peroxisomal β-oxidation in the retina and should provide perspectives for the treatment of patients.

Date:1 Jan 2019 →  31 Dec 2022
Keywords:Ophthalmology
Disciplines:Ophthalmology, Regulation of metabolism