Abstract
Purpose :
A major component of the visual transduction pathway relies on photoreceptors forming appropriate connections to their respective synaptic partners, whereby loss of photoreceptor connectivity is a leading cause of blindness. During retinal development, the different classes of photoreceptors synapse selectively to distinct targets. Cone photoreceptors synapse to the dendrites of horizontal cells (HC) and to the dendrites of cone bipolars, whereas rod photoreceptors synapse to the axon of HC and to the dendrites of rod bipolars. Although photoreceptor connectivity in the outer retina has been well-characterized, the developmental mechanism that guides their selective wiring remains unclear.
Methods :
We found different members of the Ankyrin (Anks) family, AnkB and AnkG to be highly expressed in the synaptic layer of the mouse outer retina. Anks are cytoskeletal scaffolding proteins that are known to recruit cell adhesion molecules to the membrane to mediate key signaling events during neurodevelopment. However, the function of Anks during synapse formation in the developing retina is unknown. To assess the role of Anks in photoreceptor connectivity, we crossed floxed alleles of AnkB and AnkG to a Chx10cre transgenic mouse line to conditionally delete Anks throughout the retina.
Results :
Our initial data revealed that single KO for Anks do not lead to synaptic defects; however, double KO (DKO) of AnkB and AnkG result in impaired photoreceptor connectivity. Specifically, loss of AnkB and AnkG result in retinal lamination defects where processes from HC and dendrites from rod bipolars mis-project into the outer nuclear layer. Consistent with these findings, in vivo electroretinogram recordings revealed abnormal retinal responses in AnkB and AnkG DKO compared to controls. A developmental analysis of AnkB and AnkG expression revealed that AnkB is initially expressed in HC at early stages and AnkG is expressed at later stages in rod bipolars. Based on the cell-type specific and temporal expression of AnkB and AnkG, we propose that different Anks members mediate different aspects of photoreceptors connectivity at distinct developmental time points.
Conclusions :
These findings begin to uncover a new role of Anks at the photoreceptor synapse in the outer retina. Future studies will focus on deciphering the cellular and molecular mechanisms of how Anks facilitate synapse formation in the developing retina.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.