Peroxisome Biogenesis Disorder (PBD) also known as Zellweger Spectrum Disorder (ZSD)
https://www.jlr.org/article/S0022-2275(25)00031-8/fulltext
Peroxisome Biogenesis Disorder also known as Zellweger Spectrum Disorder (ZSD) is a rare inherited condition that causes widespread organ damage, including progressive retinal degeneration leading to vision loss. ZSD is caused by mutations in the PEX genes required for the well-functioning of peroxisomes, cell structures that help produce key lipids for the brain and eyes. In this study, researchers utilised a mouse model of ZSD to investigate how peroxisome dysfunction impacts the retinal cells, specifically the retinal pigment epithelium (RPE). Using microscopy and mass spectrometry on mice of different ages, the team assessed the evolution of the disease. They detected abnormal fat changes even before any visible damage appeared. As the mice aged, analysis showed a buildup of toxic lipids and loss of certain protective ones called plasmalogen and DHA. Damage progressively spread throughout the retina, leading to RPE degeneration, local inflammation and loss of visual function. These findings suggest that lipid dysregulation in the RPE may drive retinal degeneration. These identified early changes could be potential health indicators to monitor disease evolution and therapeutic targets for treating vision loss in ZSD.