Description
Photoreceptors undergo continuous renewal to maintain visual function and retinal integrity. Each day, neighbouring retinal pigment epithelial (RPE) cells phagocytose the aged and damaged tips of photoreceptor outer segments (OS). Within the RPE, these components are degraded, while essential lipids and metabolites are recycled back to photoreceptors. This tightly regulated process supports photoreceptor survival, retinal homeostasis, and efficient phototransduction. RPE cells manage a remarkable amount of material daily, processing up to 30 OS tips per cell, each representing approximately 10% of the entire OS. Consequently, disruption of lipid homeostasis and lipid accumulation are hallmark features of dysfunctional RPE observed in retinal diseases such as Stargardt disease, choroideremia, and age-related macular degeneration.
Peroxisomes are highly dynamic membrane-bound organelles involved in lipid β-oxidation, lipid biosynthesis, hydrogen peroxide metabolism, and detoxification. Their importance in retinal health is highlighted in patients with Zellweger syndrome, a severe inherited peroxisome biogenesis disorder affecting multiple organs, including the eye. Patients with Zellweger syndrome develop retinopathy that can lead to early-onset blindness, likely caused by lipid accumulation and dysfunction in both RPE cells and photoreceptors. Despite their importance, the role of peroxisomes in RPE cells and the mechanisms linking peroxisomal dysfunction to lipid accumulation remain poorly understood.
This study aims to address this gap by investigating interactions between peroxisomes and other cellular structures in healthy RPE using animal and cellular models. Immunofluorescence imaging revealed an extensive peroxisomal network distributed throughout the cell. Electron microscopy confirmed known interactions between peroxisomes, mitochondria, and the endoplasmic reticulum and identified new type of contacts with the plasma membrane. We also observed interactions with RPE-specific organelles, including melanosomes and phagosomes, which may play important roles in lipid transport. Finally, tomographic analysis resolved tethering structures between selected organelles, providing insights into proteins potentially involved in these interactions. Together, these findings establish a foundation for future studies using induced pluripotent stem cell-derived RPE models carrying pathogenic mutations observed in patients with Zellweger syndrome with retina phenotypes.
Lay Abstract
Photoreceptor cells in the retina constantly renew themselves to maintain healthy vision. Every day, neighbouring retinal pigment epithelial (RPE) cells remove and digest damaged parts of photoreceptors while recycling useful lipids and metabolites. This demanding process is essential for retinal health and depends on the coordinated activity of many cellular organelles within the RPE. When this balance is disrupted, harmful lipid accumulation can occur, contributing to retinal diseases such as Stargardt disease, choroideremia, and age-related macular degeneration.
Peroxisomes are small cellular organelles involved in lipid metabolism, detoxification, and protection against oxidative stress. Their importance in the retina is highlighted in Zellweger syndrome, a severe inherited disorder in which defective peroxisomes lead to retinal degeneration and early blindness. However, the precise role of peroxisomes in RPE cells remains poorly understood.
This study investigates how peroxisomes interact with other cellular components inside healthy RPE cells using advanced imaging techniques, including immunofluorescence, electron microscopy, and tomography. We identified close interactions between peroxisomes and several organelles, including mitochondria, the endoplasmic reticulum, melanosomes, and phagosomes, suggesting an important role in lipid transport and cellular maintenance. These findings provide a foundation for future studies using patient-derived stem cell models of retinal disease.
| Lay Title | Unveil the Elusive Peroxisomal Network in Retinal Pigment Epithelium |
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| Role | Postdoctoral Researcher |