June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Spatiotemporal mapping of neurogenic gene expression during mammalian retinal development
Author Affiliations & Notes
  • Shabnam Majidi
    Pharmacology & Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Nathan Mundell
    Harvard Medical School, Boston, Massachusetts, United States
  • Jiyao Zhu
    Biology, Saint Louis University, Saint Louis, Missouri, United States
  • Rebecca Girresch
    Biology, Saint Louis University, Saint Louis, Missouri, United States
  • Nick Steinauer
    Pharmacology & Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Aurore Valfort
    St Louis College of Pharmacy, Saint Louis, Missouri, United States
  • Suomia Abuirqeba
    Pharmacology & Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Amina Kamerić
    Pharmacology & Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Monideepa Sengupta
    Yale University School of Medicine, New Haven, Connecticut, United States
  • Grant Kolar
    Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Judy M Ogilvie
    Biology, Saint Louis University, Saint Louis, Missouri, United States
  • Colin Flaveny
    Pharmacology & Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Footnotes
    Commercial Relationships   Shabnam Majidi, None; Nathan Mundell, None; Jiyao Zhu, None; Rebecca Girresch, None; Nick Steinauer, None; Aurore Valfort, None; Suomia Abuirqeba, None; Amina Kamerić, None; Monideepa Sengupta, None; Grant Kolar, None; Judy Ogilvie, None; Colin Flaveny, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 234. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shabnam Majidi, Nathan Mundell, Jiyao Zhu, Rebecca Girresch, Nick Steinauer, Aurore Valfort, Suomia Abuirqeba, Amina Kamerić, Monideepa Sengupta, Grant Kolar, Judy M Ogilvie, Colin Flaveny; Spatiotemporal mapping of neurogenic gene expression during mammalian retinal development. Invest. Ophthalmol. Vis. Sci. 2021;62(8):234.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The prevalence of blindness due to retinal injury has inspired widespread efforts to develop new treatments. Despite significant advances made in retinal cell transplantation, achieving proper repair of existing retinal tissue remains a significant obstacle. A new and exciting alternative strategy involves the stimulation of retinal regeneration from a patient’s own stem-like cells. Müller glia are the only retinal cell type to express the orphan nuclear receptor TLX, a master regulator of neuronal stemness. Due to its enriched expression in Müller glia and the potential for pharmacologic manipulation, we hypothesize that TLX may serve as an ideal therapeutic target for stimulating repair and regeneration in the mammalian retina.

Methods : A transgenic mouse model was developed wherein Müller glia express a YFP reporter transgene, allowing us to effectively track Müller glia through 8 key stages of retinal development that coincide with available single cell RNA-sequencing (scRNA) datasets. Freshly enucleated eye cups were harvested from wild type and transgenic mice at each key developmental stage. All eyecups were fixed with 4% paraformaldehyde, washed with PBS and stored in 30% sucrose/PBS solution. Eyecups were cryopreserved and 12 um cryosections obtained for immunofluorescence detecting TLX and markers of Müller glia and other retinal cell types. Imaging was performed via confocal microscopy.

Results : TLX is highly expressed in the embryonic retinal progenitor cells during mouse retinal development via scRNA sequencing data. Müller glia start expressing TLX mRNA and protein at postnatal day 5 (P5) in mouse retina. By P8, TLX mRNA and protein are solely expressed by Müller glial cells in the retina.

Conclusions : Overall, we have temporospatially mapped the expression of TLX from embryonic retinal progenitor cells to fully differentiated retinal cell types of the adult retina. We find that TLX expression becomes restricted to Muller glia over the course of mouse retinal development. Collectively, these studies provide a foundation of understanding for the potential molecular mechanisms implicated in the retinal regenerative capacity of mammalian Müller glia and provide further basis for the study of TLX as a candidate target for retinal regeneration.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×