July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Human pluripotent stem cell derived retinal organoids reveal an important role for IMPG1 and CD44 in the development of photoreceptors and their synaptic connections
Author Affiliations & Notes
  • Majed Felemban
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Birthe Dorgau
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Nicola Hunt
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Joseph Collin
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • David Steel
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Susan Lindsay
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Carla Bernadette Mellough
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Majlinda Lako
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
  • Footnotes
    Commercial Relationships   Majed Felemban, None; Birthe Dorgau, None; Nicola Hunt, None; Joseph Collin, None; David Steel, None; Susan Lindsay, None; Carla Mellough, None; Majlinda Lako, None
  • Footnotes
    Support  ERC Grant 614620, RPFB Grant 6R559
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1984. doi:
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      Majed Felemban, Birthe Dorgau, Nicola Hunt, Joseph Collin, David Steel, Susan Lindsay, Carla Bernadette Mellough, Majlinda Lako; Human pluripotent stem cell derived retinal organoids reveal an important role for IMPG1 and CD44 in the development of photoreceptors and their synaptic connections. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1984.

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

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Abstract

Purpose : The extracellular matrix (ECM) plays major roles in numerous cellular processes during retinal development. Although several ECM components have been studied in the mature and developing retina of many species, there has been no detailed analysis of the ECM distribution during human retinal ontogenesis and so the functional importance of many human ECM components is poorly understood. In this study, the expression of key ECM components in developing human retina and retinal organoids derived from human pluripotent stem cells (hPSCs) was studied.

Methods : Using immunocytochemistry, we studied the spatio-temporal expression profile of key ECM molecules in the developing human eye, adult human retina and retinal organoids generated from hPSCs. The following ECM components were investigated: Versican (VCAN), Brevican (BCAN), Interphotoreceptor Matrix Proteoglycan 1 (IMPG1), Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) and cluster of differentiation 44 (CD44). In order to investigate the role of IMPG1 and CD44 in photoreceptor differentiation, blocking antibodies to IMPG1 and CD44 were added to the culture media during 3D retinal differentiation of hPSCs.

Results : Expression of VCAN, BCAN, IMPG1 and IMPG2 were detected in the developing interphotoreceptor matrix (IPM). Expression of VCAN, BCAN and IMPG1 was conserved between the developing and adult human retina and hPSC-derived retinal organoids. CD44 blocking had a negative impact on rod development, IPM formation, and the establishment of synaptic connectivity between the photoreceptors and other retinal cells. In contrast, blocking of IMPG1 resulted in disorganisation of cone photoreceptors.

Conclusions : The study showed a conserved expression pattern for VCAN, BCAN and IMPG1 and throughout the period of retinal development studied and in the adult human retina which suggests that they may be important for photoreceptor development and function. Blocking of CD44 and IMPG1 in hPSC-derived retinae resulted in the disorganisation of photoreceptor development as well as outer plexiform synaptic connections suggesting a crucial role for CD44 and IMPG1 in both processes. Overall, the data provide convincing evidence on the utility of pluripotent stem cell derived retinal organoids in furthering understanding of the factors that drive human retinal ontogenesis.

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

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