| First Author | Swinkels D | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 1 | PubMed ID | 35011723 |
| Mgi Jnum | J:318726 | Mgi Id | MGI:6852836 |
| Doi | 10.3390/cells11010161 | Citation | Swinkels D, et al. (2022) Cell Type-Selective Loss of Peroxisomal beta-Oxidation Impairs Bipolar Cell but Not Photoreceptor Survival in the Retina. Cells 11(1) |
| abstractText | Retinal degeneration is a common feature in peroxisomal disorders leading to blindness. Peroxisomes are present in the different cell types of the retina; however, their precise contribution to retinal integrity is still unclear. We previously showed that mice lacking the central peroxisomal beta-oxidation enzyme, multifunctional protein 2 (MFP2), develop an early onset retinal decay including photoreceptor cell death. To decipher the function of peroxisomal beta-oxidation in photoreceptors, we generated cell type selective Mfp2 knockout mice, using the Crx promotor targeting photoreceptors and bipolar cells. Surprisingly, Crx-Mfp2(-/-) mice maintained photoreceptor length and number until the age of 1 year. A negative electroretinogram was indicative of preserved photoreceptor phototransduction, but impaired downstream bipolar cell signaling from the age of 6 months. The photoreceptor ribbon synapse was affected, containing free-floating ribbons and vesicles with altered size and density. The bipolar cell interneurons sprouted into the ONL and died. Whereas docosahexaenoic acid levels were normal in the neural retina, levels of lipids containing very long chain polyunsaturated fatty acids were highly increased. Crx-Pex5(-/-) mice, in which all peroxisomal functions are inactivated in photoreceptors and bipolar cells, developed the same phenotype as Crx-Mfp2(-/-) mice. In conclusion, the early photoreceptor death in global Mfp2(-/-) mice is not driven cell autonomously. However, peroxisomal beta-oxidation is essential for the integrity of photoreceptor ribbon synapses and of bipolar cells. |
