June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A subset of retinal ganglion cells that control angiogenesis requires TBX3 for their formation
Author Affiliations & Notes
  • Andrea Sophia Viczian
    Ophthalmology & Visual Sciences, SUNY Upstate Medical University, Syracuse, New York, United States
  • Anne M Moon
    Molecular and Functional Genomics, Geisinger Health, Danville, Pennsylvania, United States
  • Michael E Zuber
    Ophthalmology & Visual Sciences, SUNY Upstate Medical University, Syracuse, New York, United States
  • Footnotes
    Commercial Relationships   Andrea Viczian None; Anne Moon None; Michael Zuber None
  • Footnotes
    Support  EY034277
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3627. doi:
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    • Get Citation

      Andrea Sophia Viczian, Anne M Moon, Michael E Zuber; A subset of retinal ganglion cells that control angiogenesis requires TBX3 for their formation. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3627.

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

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Abstract

Purpose : We previously determined that the T-box factor, Tbx3, is required for retinal angiogenesis due to a loss of a subset of retinal ganglion cells. The purpose of this study was to determine when retinal ganglion cells are first affected by Tbx3 loss and a molecular mechanism to explain the vascular defect found in these mice.

Methods : Conditional removal of Tbx3 from retinal progenitors was done using the optic cup-Cre recombinase driver, BAC-Dkk3-CRE. Immunohistostaining and imaging were performed. Cell counts were performed double-blind to the sample types and statistical analysis used Prism v9.5.

Results : Tbx3 is expressed when retinal ganglion cells are born at E10.5. In the conditional knockout retinas at E13.5, we found no statistically significant change in the quintessential transcription factor required for retinal ganglion cell formation (Atoh7: WT, 282±8.6; cKO, 213±41 cells/retina), yet a statistically significant reduction of cells expressing neural marker, Tubb3 (WT, 0.14±0.02; cKO, 0.07±0.01 percent of retinal area, p=0.04), and in ganglion cells detected by RXR-gamma (WT, 163±4; cKO, 58±17 cells/retina; p=0.015) and Tbx5 (WT, 173±15; cKO, 57±18 cells/retina, p=0.005) antibodies. We also found a decrease in a transcription factor essential for the formation of intrinsically photosensitive retinal ganglion cells (ipRGCs), Tbr2 (WT, 1±0.07; cKO, 0.7±0.06 normalized to average WT; p=0.02). This is consistent with our previous study, which showed a significant loss of ipRGCs in Tbx3 conditional knockout retinas. At birth, when astrocytes begin migrating into the retina, we found a reduction in retinal ganglion cell expression of sonic hedgehog (Shh: WT, 5±0.1; cKO, 2.6±0.3 densitometry of western, p=0.01), which is required for astrocyte proliferation. Consistent with this finding, in a pilot study, we also observed a reduction in astrocytes expressing proliferation marker, Ki67, and a subsequent reduction of astrocytes in the retina.

Conclusions : Our working hypothesis is that Tbx3 is required by a subset of retinal ganglion cells that draw in astrocytes to form the mature retinal vasculature. In the Tbx3 cKO retina, we observed loss of cells expressing RGC markers, together with a reduction in Shh, and fewer proliferating astrocytes, which adds evidence to support our hypothesis. Future studies will determine which types of RGCs are affected by Tbx3 loss.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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