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Phagocytosis in the retina promotes local insulin production in the eye

J. Iker Etchegaray, Shannon Kelley, Kristen Penberthy, Laura Karvelyte, Yosuke Nagasaka, Sofia Gasperino, Soumen Paul, Vikram Seshadri, Michael Raymond, Ana Royo Marco, et al.
(2023) NATURE METABOLISM. 5(2). p.207-218
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Abstract
The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (‘loss of function’) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (‘gain of function’) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.
Keywords
ROD OUTER SEGMENTS, PIGMENT-EPITHELIUM, MESSENGER-RNA, CONE SURVIVAL, RAT RETINA, RECEPTOR, GENE, STARVATION, MUTATION, PROTEIN

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Citation

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MLA
Iker Etchegaray, J., et al. “Phagocytosis in the Retina Promotes Local Insulin Production in the Eye.” NATURE METABOLISM, vol. 5, no. 2, 2023, pp. 207–18, doi:10.1038/s42255-022-00728-0.
APA
Iker Etchegaray, J., Kelley, S., Penberthy, K., Karvelyte, L., Nagasaka, Y., Gasperino, S., … Ravichandran, K. (2023). Phagocytosis in the retina promotes local insulin production in the eye. NATURE METABOLISM, 5(2), 207–218. https://doi.org/10.1038/s42255-022-00728-0
Chicago author-date
Iker Etchegaray, J., Shannon Kelley, Kristen Penberthy, Laura Karvelyte, Yosuke Nagasaka, Sofia Gasperino, Soumen Paul, et al. 2023. “Phagocytosis in the Retina Promotes Local Insulin Production in the Eye.” NATURE METABOLISM 5 (2): 207–18. https://doi.org/10.1038/s42255-022-00728-0.
Chicago author-date (all authors)
Iker Etchegaray, J., Shannon Kelley, Kristen Penberthy, Laura Karvelyte, Yosuke Nagasaka, Sofia Gasperino, Soumen Paul, Vikram Seshadri, Michael Raymond, Ana Royo Marco, Jonathan Pinney, Marta Stremska, Brady Barron, Christopher Lucas, Nishikant Wase, Yong Fan, Emil Unanue, Bijoy Kundu, Tal Burstyn-Cohen, Justin Perry, Jayakrishna Ambati, and Kodi Ravichandran. 2023. “Phagocytosis in the Retina Promotes Local Insulin Production in the Eye.” NATURE METABOLISM 5 (2): 207–218. doi:10.1038/s42255-022-00728-0.
Vancouver
1.
Iker Etchegaray J, Kelley S, Penberthy K, Karvelyte L, Nagasaka Y, Gasperino S, et al. Phagocytosis in the retina promotes local insulin production in the eye. NATURE METABOLISM. 2023;5(2):207–18.
IEEE
[1]
J. Iker Etchegaray et al., “Phagocytosis in the retina promotes local insulin production in the eye,” NATURE METABOLISM, vol. 5, no. 2, pp. 207–218, 2023.
@article{01H77GEVKAKFEMWGFJEFDKPRXY,
  abstract     = {{The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (‘loss of function’) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (‘gain of function’) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.}},
  author       = {{Iker Etchegaray, J. and  Kelley, Shannon and  Penberthy, Kristen and  Karvelyte, Laura and  Nagasaka, Yosuke and  Gasperino, Sofia and  Paul, Soumen and  Seshadri, Vikram and  Raymond, Michael and  Marco, Ana Royo and  Pinney, Jonathan and  Stremska, Marta and  Barron, Brady and  Lucas, Christopher and  Wase, Nishikant and  Fan, Yong and  Unanue, Emil and  Kundu, Bijoy and  Burstyn-Cohen, Tal and  Perry, Justin and  Ambati, Jayakrishna and Ravichandran, Kodi}},
  issn         = {{2522-5812}},
  journal      = {{NATURE METABOLISM}},
  keywords     = {{ROD OUTER SEGMENTS,PIGMENT-EPITHELIUM,MESSENGER-RNA,CONE SURVIVAL,RAT RETINA,RECEPTOR,GENE,STARVATION,MUTATION,PROTEIN}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{207--218}},
  title        = {{Phagocytosis in the retina promotes local insulin production in the eye}},
  url          = {{http://doi.org/10.1038/s42255-022-00728-0}},
  volume       = {{5}},
  year         = {{2023}},
}
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