June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
STZ is toxic to rat retinal progenitors and suppresses their expansion
Author Affiliations & Notes
  • Yu Lin
    Sichuan University West China Hospital, Chengdu, Sichuan, China
  • Xiang Ren
    Sichuan University West China Hospital, Chengdu, Sichuan, China
  • Danian Chen
    Sichuan University West China Hospital, Chengdu, Sichuan, China
  • Footnotes
    Commercial Relationships   Yu Lin None; Xiang Ren None; Danian Chen None
  • Footnotes
    Support  National Natural Science Foundation of China (81870665)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2447 – F0391. doi:
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      Yu Lin, Xiang Ren, Danian Chen; STZ is toxic to rat retinal progenitors and suppresses their expansion. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2447 – F0391.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : STZ is toxic to pancreatic b cells and thus can induce type 1 diabetes, but if it has any direct effects on retinal cells is unknown. The purpose of this study is to investigate the effects of systemic administered STZ on the retina of neonatal rats.

Methods : STZ or citrate buffer (control) were subcutaneously injected into neonatal rats at postnatal day 1, 3, and 5 (P1/3/5). Electroretinogram (ERG), hematoxylin and eosin (H&E) staining, immunofluorescent staining, flow cytometry, and RNA sequencing were performed to evaluate the effects of STZ on retinal function and structure, and retinal cell differentiation at different time-points after STZ administration, from P2-P70.

Results : At P21, STZ reduced the amplitudes of dark-adapted a wave and b wave, as well as the total oscillatory potentials (OPs) energy. HE staining showed abnormal retinal structures from P5, including rosettes at the peripheral retina and ONL extrusions at the central retina. The retina is much thinner, including ONL and INL. Immunofluorescent staining revealed that the numbers of early-born retinal cell types (ganglion cells, cone, horizontal cells and amacrine cells) were not changed, but the late-born retinal cell types (rod, bipolar cells and Müller cells) were significantly reduced. STZ induced cell death (TUNEL+ or active caspase 3+) of retinal progenitor cells (RPCs), from P2-P5 (mainly at P3-P4). EdU labeling and Ki67 staining found that STZ suppressed the proliferation of RPCs and delayed the cell cycle exit of RPCs. Flow cytometry showed that the G2/M phase of STZ rats reduced significantly. STZ also delayed the development of retinal deep vascular plexus (DVP) at P10.

Conclusions : STZ is toxic to rat RPCs, induces cell death and cell cycle arrest of this cell type.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.




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