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- Author
-
N. Milićević
- Title
- Circadian regulation of the retinal pigment epithelium–photoreceptor complex
- Supervisors
-
A.A.B. Bergen
M.P. Felder-Schmittbuhl - Award date
- 1 April 2020
- Number of pages
- 121
- ISBN
- 9789464021370
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Photoreceptors lie in close contact with the retinal pigment epithelium (RPE) forming a single multi-functional unit central to vision and retina survival. Little is known about the physiological functions regulated by the circadian clock in the RPE – photoreceptor complex. The rhythmic phagocytosis of photoreceptor outer segments (POS) is essential for retinal health. In this thesis, we found no rhythm in phagocytosis of POS in mice carrying a double clock gene Per1, Per2 mutation. There were no obvious transcriptional links between the circadian clock and POS phagocytosis in wild-type mouse photoreceptors. We found that most of the phagocytosis machinery is rhythmic on a transcriptional, protein and functional level in ARPE-19 (RPE) cells. This machinery is modulated by POS and the clock gene REV-ERBα. We found that other aspects of RPE physiology also oscillate. Our results suggested that RPE-mediated ion transport is rhythmic via the sodium-potassium-chloride cotransporter NKCC1. We also found a rhythm in RPE-mediated transport of lactate via the monocarboxylate transporter SLC16A1 (MCT1). In contrast, we found no evidence of rhythmic glucose transport by the RPE. This thesis sheds some light on the regulation of POS phagocytosis and expands the repertoire of circadian clock-regulated physiology of the RPE-photoreceptor complex.
- Persistent Identifier
- https://hdl.handle.net/11245.1/89e381a4-3b4c-494b-b4f1-ab4100a59a24
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General Introduction
Chapter 2: Rev-Erbα and photoreceptor outer segments modulate the circadian clock in retinal pigment epithelial cells
Chapter 3: Does the circadian clock make RPE-mediated ion transport “tick” via SLC12A2 (NKCC1)?
Chapter 4: The circadian clock regulates RPE-mediated lactate transport via SLC16A1 (MCT1)
Chapter 5: Core circadian clock genes Per1 and Per2 drive the rhythm in photoreceptor outer segment phagocytosis and photoreceptor DNA repair
Chapter 6: General discussion
Chapter 7: Thesis summary; Résumé de thèse; Nederlandse samenvatting; Thesis abstract
Appendix: PhD portfolio; Acknowledgements
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