June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Deciphering the Role of Protocadherin 9 in Synaptic Specificity of the Outer Retina
Author Affiliations & Notes
  • Marlon Mattos
    Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Caitlin Bagnetto
    Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Cesiah Gomez
    Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Debalina Goswami-Sewell
    Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Elizabeth Zuniga-Sanchez
    Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    Department of Neuroscience, Baylor College of Medicine Department of Neuroscience, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Marlon Mattos None; Caitlin Bagnetto None; Cesiah Gomez None; Debalina Goswami-Sewell None; Elizabeth Zuniga-Sanchez None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3633. doi:
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      Marlon Mattos, Caitlin Bagnetto, Cesiah Gomez, Debalina Goswami-Sewell, Elizabeth Zuniga-Sanchez; Deciphering the Role of Protocadherin 9 in Synaptic Specificity of the Outer Retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3633.

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

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Abstract

Purpose : Establishing proper wiring between photoreceptors and their synaptic partners is critical for normal retinal circuitry. Failure to form proper synaptic connections disrupts the transmission of visual information and impairs visual function. In the outer retina, the different classes of photoreceptors synapse to distinct bipolar targets. Cone photoreceptors synapse to cone bipolars whereas rod photoreceptors synapse to rod bipolars. Although several cell adhesion molecules have been implicated in rod-to-rod bipolar connectivity, little is known about the key molecules that mediate cone-to-cone bipolar specificity.

Methods : We found distinct cell adhesion molecules belonging to the non-clustered Protocadherin family to be expressed in cone bipolars but not rod bipolars. Protocadherin 9 (Pcdh9) is highly expressed in the developing synaptic layer and restricted to cone bipolars. To assess the function of Pcdh9 in synaptic connectivity, we crossed a floxed allele of Pcdh9 with a Chx10cre transgenic mouse line to conditionally remove Pcdh9 throughout the developing retina. We refer to this cross as Pcdh9 CKO. Retinas from Pcdh9 CKO and controls were fixed and analyzed for synaptic defects at various developmental ages using available antibodies.

Results : Disruption of Pcdh9 results in cone bipolars failing to extend their dendrites to the synaptic layer or OPL. We also observe that cone terminals have an abnormal morphology due to loss of Pcdh9. In addition to the morphological defects, we also observe defects in synaptic connectivity where there is a significant decrease in protein expression of the pre-synaptic marker Bassoon in Pcdh9 CKO compared to controls. These data suggest that Pcdh9 may have an important role in mediating connectivity between cone photoreceptors and their cone bipolar targets.

Conclusions : Our findings begin to highlight a new role for Pcdh9 in synaptic connectivity of the cone pathway. Future work will focus on disseminating the cellular and molecular mechanisms of Pcdh9 in synaptic specificity of the developing retina.

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

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