July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Investigating Lsd1 in proper retinal development and retinoblastoma differentiation
Author Affiliations & Notes
  • Salma Ferdous
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Hans Grossniklaus
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Eldon E Geisert
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • J M Nickerson
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Salma Ferdous, None; Hans Grossniklaus, None; Eldon Geisert, None; J Nickerson, None
  • Footnotes
    Support  R01EY021592, R01EY016470, 4T32GM008490-24, and 4T32EY006360-32
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1627. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Salma Ferdous, Hans Grossniklaus, Eldon E Geisert, J M Nickerson; Investigating Lsd1 in proper retinal development and retinoblastoma differentiation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1627.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The purpose of this study was to determine the role of lysine specific demethylase 1 (Lsd1) in proper retinal differentiation via the regulation of RNA expression. We mapped a trans quantitative trait locus (transQTL) that controls differential exon expression in the BXD mouse strains. Within the visual system, Lsd1 is expressed in late progenitor retinal cells and inhibition of Lsd1 blocks rod photoreceptor development (Popova et al. Mol Neurobiol 53:4563–4581). Proper retinal differentiation is vital for normal visual function, but aberrantly occurs in retinoblastoma, the most common childhood primary intraocular tumor. Several hallmark features of retinoblastoma tumors, such as rosettes and fleurettes mimic photoreceptor differentiation. Because rosettes and fleurettes mimic general retinal differentiation, we investigated the role of Lsd1 in normal murine retinal development and human retinoblastoma tumors.

Methods : We conducted linkage analysis using a GeneNetwork.org dataset from BXD retinal mRNA run on Affymetrix ST2.0 Exon microarrays (King et al. Mol Vis 21:1235-1251). We conducted immunohistochemistry (IHC) and western blotting (WB) on C57BL/6J and DBA/2J mice and we tested Lsd1 heterozygous mice using several techniques, including electroretinogram (ERG), SDOCT, Fundus photography, IHC, WB, and H&E staining to assess ocular health. Additionally, we conducted IHC on enucleated human eyes from retinoblastoma patients.

Results : Within the transQTL, Lsd1 is the leading candidate because of its epigenetic role in regulating both gene activation and repression programs and terminal neuron differentiation. WB at a developmentally critical time, post-natal day 7, DBA mice show higher Lsd1 protein levels than C57, but IHC shows similar localization patterns between the mouse strains. In mature retinas, Lsd1 is expressed in the majority of cells within the 3 nuclear layers but is depressed in rods (Figure 1). Lsd1 heterozygous mice do not display gross morphological retinal defects in SDOCT, Fundus photos, IHC, or H&E staining and ERGs to test retinal function appear normal. Within retinoblastoma tumors, Lsd1 is highly expressed in differentiated areas, but absent in undifferentiated areas (Figure 2).

Conclusions : These experiments show Lsd1 involvement in the differentiation of certain retinal cell subtypes and possible contribution to the differentiation and aggression of retinoblastoma tumors.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

 

×
×

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.

×