Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors

Kayla F. Titialii-Torres, Ann C. Morris

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Diabetes is linked to various long-term complications in adults, such as neuropathy, nephropathy and diabetic retinopathy. Diabetes poses additional risks for pregnant women, because glucose passes across the placenta, and excess maternal glucose can result in diabetic embryopathy. While many studies have examined the teratogenic effects of maternal diabetes on fetal heart development, little is known about the consequences of maternal hyperglycemia on the development of the embryonic retina. To address this question, we investigated retinal development in two models of embryonic hyperglycemia in zebrafish. Strikingly, we found that hyperglycemic larvae displayed a significant reduction in photoreceptors and horizontal cells, whereas other retinal neurons were not affected. We also observed reactive gliosis and abnormal optokinetic responses in hyperglycemic larvae. Further analysis revealed delayed retinal cell differentiation in hyperglycemic embryos that coincided with increased reactive oxygen species (ROS). Our results suggest that embryonic hyperglycemia causes abnormal retinal development via altered timing of cell differentiation and ROS production, which is accompanied by visual defects. Further studies using zebrafish models of hyperglycemia will allow us to understand the molecular mechanisms underlying these effects.

Original languageEnglish
Article numberjcs259187
JournalJournal of Cell Science
Volume135
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Publisher Copyright:
© 2022. Published by The Company of Biologists Ltd

Funding

The authors would like to thank Evelyn Turnbaugh and Lucas Vieira Francisco for exceptional zebrafish care. We also thank Dr Hannah Henson for conceptual input and Dr Cagney Coomer for editorial input. This work was supported by grants from the NIH National Eye Institute (R01EY021769, to A.C.M.), the WUSTL Diabetes Research Center, an NIH-funded program (P30DK020579) supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; to A.C.M.), the National Science Foundation Bridge to the Doctorate Fellowship (NSF HRD 2004710, to K.F.T.-T.), the University of Kentucky Lyman T. Johnson graduate fellowship (to K.F.T.-T.), the UK Biology Merit Fellowship (to K.F.T.-T.), and a Gertrude F. Ribble Mini Grant (to K.F.T.-T.). Deposited in PMC for release after 12 months. This work was supported by grants from the NIH National Eye Institute (R01EY021769, to A.C.M.), the WUSTL Diabetes Research Center, an NIH-funded program (P30DK020579) supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; to A.C.M.), the National Science Foundation Bridge to the Doctorate Fellowship (NSF HRD 2004710, to K.F.T.-T.), the University of Kentucky Lyman T. Johnson graduate fellowship (to K.F.T.-T.), the UK Biology Merit Fellowship (to K.F.T.-T.), and a Gertrude F. Ribble Mini Grant (to K.F.T.-T.). Deposited in PMC for release after 12 months.

FundersFunder number
Pan-Massachusetts Challenge
Biology Merit Fellowship
University of Kentucky
WUSTL Diabetes Research Center
National Institute of Diabetes and Digestive and Kidney DiseasesP30DK020579
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of ChinaHRD 2004710
NIH-funded University of Kentucky Center for Cancer and MetabolismP30DK020579
National Eye Institute/National Institutes of HealthR01EY021769

    Keywords

    • Diabetes
    • Hyperglycemia
    • Photoreceptors
    • Retina
    • Zebrafish

    ASJC Scopus subject areas

    • Cell Biology

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