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Author
- Chao, Jennifer R2
- Engel, Abbi L2
- Huang, Jiancheng2
- Zhao, Chen2
- Brock, Daniel C1
- Brockerhoff, Susan E1
- Burrell, Anika L1
- Chambers, Zachary S1
- Cleghorn, Whitney M1
- Dinterman, Marlee1
- Djukovic, Danijel1
- Giarmarco, Michelle M1
- Gong, Kaizheng1
- Gu, Haiwei1
- Hauer, Allison1
- Hurley, James B1
- Jankowski, Connor1
- Knight, Kaitlen1
- Kollman, Justin M1
- Liu, Xinnong1
- Lohner, Daniel1
- Manson, Megan A1
- Raftery, Daniel1
Keyword
- amino acid3
- retinal metabolism3
- metabolism2
- mitochondrial metabolism2
- retina2
- age-related macular degeneration (AMD)1
- cell metabolism1
- glucose metabolism1
- IHC1
- immunohistochemistry1
- IMPDH1
- inner segment1
- inosine monophosphate dehydrogenase1
- IS1
- metabolic filaments1
- metabolic regulation1
- metabolic tracer1
- metabolomics1
- nitrogen metabolism1
- oxidative stress1
- photoreceptor metabolism1
- photoreceptors1
- proline1
- TEM1
- Zebrafish1
Neurobiology
4 Results
- Research ArticleOpen Access
A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells
Journal of Biological ChemistryVol. 298Issue 1101441Published online: November 19, 2021- Whitney M. Cleghorn
- Anika L. Burrell
- Michelle M. Giarmarco
- Daniel C. Brock
- Yekai Wang
- Zachary S. Chambers
- and others
Cited in Scopus: 2Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Dominant mutations in human IMPDH1 cause photoreceptor degeneration for reasons that are unknown. Here, we sought to provide some foundational information on Impdh1a in the zebrafish retina. We found that in zebrafish, gene subfunctionalization due to ancestral duplication resulted in a predominant retinal variant expressed exclusively in rod and cone photoreceptors. This variant is structurally and functionally similar to the human IMPDH1 retinal variant and shares a reduced sensitivity to GTP-mediated inhibition. - MetabolismOpen Access
The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected
Journal of Biological ChemistryVol. 295Issue 8p2324–2335Published online: January 17, 2020- Rong Xu
- Brianna K. Ritz
- Yekai Wang
- Jiancheng Huang
- Chen Zhao
- Kaizheng Gong
- and others
Cited in Scopus: 13Defects in energy metabolism in either the retina or the immediately adjacent retinal pigment epithelium (RPE) underlie retinal degeneration, but the metabolic dependence between retina and RPE remains unclear. Nitrogen-containing metabolites such as amino acids are essential for energy metabolism. Here, we found that 15N-labeled ammonium is predominantly assimilated into glutamine in both the retina and RPE/choroid ex vivo. [15N]Ammonium tracing in vivo show that, like the brain, the retina can synthesize asparagine from ammonium, but RPE/choroid and the liver cannot. - MetabolismOpen Access
Proline mediates metabolic communication between retinal pigment epithelial cells and the retina
Journal of Biological ChemistryVol. 294Issue 26p10278–10289Published online: May 19, 2019- Michelle Yam
- Abbi L. Engel
- Yekai Wang
- Siyan Zhu
- Allison Hauer
- Rui Zhang
- and others
Cited in Scopus: 42The retinal pigment epithelium (RPE) is a monolayer of pigmented cells between the choroid and the retina. RPE dysfunction underlies many retinal degenerative diseases, including age-related macular degeneration, the leading cause of age-related blindness. To perform its various functions in nutrient transport, phagocytosis of the outer segment, and cytokine secretion, the RPE relies on an active energy metabolism. We previously reported that human RPE cells prefer proline as a nutrient and transport proline-derived metabolites to the apical, or retinal, side. - MetabolismOpen Access
Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side
Journal of Biological ChemistryVol. 292Issue 31p12895–12905Published online: June 14, 2017- Jennifer R. Chao
- Kaitlen Knight
- Abbi L. Engel
- Connor Jankowski
- Yekai Wang
- Megan A. Manson
- and others
Cited in Scopus: 55Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with 13C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids.