Opposite Roles of MerTK Ligands Gas6 and Protein S During Retinal Phagocytosis
1Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, Paris, F-75012, France. emeline.nandrot@inserm.fr.
Abstract:
MerTK is required for photoreceptor outer segment (POS) phagocytosis by retinal pigment epithelial (RPE) cells, a diurnal function essential for vision maintenance. In vivo, MerTK is stimulated at the time of the phagocytic peak through an intracellular signaling pathway. However, MerTK ligands Gas6 and Protein S are expressed in both RPE cells and photoreceptors, and at least one of them required for phagocytosis to occur. Still, their exact role in the retina was not clear until recently. This review combines results from different studies to shed the light on a tissue-specific regulation of MerTK function by its ligands. Indeed, with opposite effects on RPE phagocytosis and changes in their expression levels around the time of POS uptake, Gas6 and Protein S may contribute to the tight control of the acute phagocytic peak in the retina.
Insights
MerTK signaling in retinal pigment epithelial cells is crucial for vision maintenance. This review clarifies how MerTK ligands, Gas6 and Protein S, regulate photoreceptor outer segment phagocytosis.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Retinal pigment epithelial (RPE) cells perform diurnal phagocytosis of photoreceptor outer segments (POS), a process vital for vision.
- MerTK (Mer tyrosine kinase) is essential for this phagocytosis, activated via intracellular signaling pathways during peak phagocytic times.
- MerTK ligands, Gas6 and Protein S, are present in the retina, but their specific roles in POS uptake were previously unclear.
Purpose of the Study:
- To elucidate the tissue-specific regulation of MerTK function by its ligands, Gas6 and Protein S, within the retinal context.
- To integrate findings from various studies to understand the precise roles of Gas6 and Protein S in RPE phagocytosis.
- To explain how these ligands contribute to the diurnal peak of POS uptake in the retina.
Main Methods:
- Literature review synthesizing data from multiple research studies.
- Analysis of expression patterns of MerTK, Gas6, and Protein S in RPE cells and photoreceptors.
- Examination of the functional effects of Gas6 and Protein S on RPE phagocytic activity.
Main Results:
- Gas6 and Protein S exhibit opposing effects on RPE phagocytosis.
- Expression levels of Gas6 and Protein S fluctuate around the time of POS uptake.
- These ligands are involved in the tissue-specific regulation of MerTK activity in the retina.
Conclusions:
- Gas6 and Protein S play critical, distinct roles in regulating MerTK-mediated phagocytosis in the retina.
- The dynamic interplay between MerTK ligands contributes to the precise temporal control of the phagocytic peak.
- Understanding this regulation is key to maintaining retinal health and vision.
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