July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Genetic Profiling of S- and M-Cone Photoreceptors
Author Affiliations & Notes
  • Wei Li
    Retinal Neurophysiology Section, NEI, Bethesda, Maryland, United States
  • Vincent Kunze
    Retinal Neurophysiology Section, NEI, Bethesda, Maryland, United States
  • Juan Angueyra
    Retinal Neurophysiology Section, NEI, Bethesda, Maryland, United States
  • Li Jia
    Scientific Review Branch, NINDS, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Wei Li, None; Vincent Kunze, None; Juan Angueyra, None; Li Jia, None
  • Footnotes
    Support  NEI intramural research program
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1010. doi:
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      Wei Li, Vincent Kunze, Juan Angueyra, Li Jia; Genetic Profiling of S- and M-Cone Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1010.

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

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Abstract

Purpose : Mammalians have two major types of photoreceptors in the retina: rods, specialized for vision in dim-light, and cones for vision in well-lit conditions and the perception of color. Most mammals have two cone types, namely S- and M-cones. They diverge in their sensitivity to different wavelengths of light, based on their expression of different light-sensitive proteins: S-opsin for blue light and M-opsin for green light. The purpose of this project is to identify genetic differences in cones in addition to their opsins and, more specifically, to find molecules that are potentially involved in cone synapse formation.

Methods : To identify molecular signatures of different cone types, we used single cell RNA-seq to obtain complete genetic profiles of S- and M-cones. For this study, we used the 13-lined ground squirrel that, in contrast to mouse, is diurnal and has a cone-dominated retina. The two cone types are morphologically indistinguishable, so we developed a protocol to dissociate and label live cells with an antibody targeting the extracellular domain of S-cones We then manually collected single cells for single cell sequencing.

Results : We first demonstrated that there are molecule(s) other than S-opsin necessary for proper connection of S-cones. Normally, the dendrites of the S-cone bipolar cell (SCBC), an interneuron that relays S-cone signals to downstream neurons, exclusively contact S-cones. However, genetic disruption of the normal S- and M-opsin expression pattern in different knockout mice failed to alter S-cone to SCBC connection pattern, suggesting other molecular cues for the development and maintenance of such connections.

Single cell sequencing analysis reveals differentially expressed genes that define cone identity beyond their expression of S- or M-opsins. We show in situ hybridization and immunohistochemical evidence for some of the differentially expressed genes (DEGs). We identified two S-cone specific cell-adhesion molecules that are known to play roles in synapse assembly in the brain.

Conclusions : Our results can help to understand circuit formation in the retina and synapse assembly in the nervous system. For clinical applications, this could be useful for future works that aim to replace or rewire photoreceptors in retinal degenerative diseases.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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