Jessica Garcia, a former student in the lab is now a medical student at University of Washington School of Medicine. Last week she participated in her white coat ceremony, and we are so, very proud of her.
Jessica Garcia is this year’s University of Utah Student Veteran of the Year. Jessica is an undergraduate student in the lab exploring the OFF-layer branches of ON cone bipolar cells in early retinal degeneration.
Jessica came to us by way of service with the US Navy, where she served as an aviation technician before attending the University of Utah.
Congratulations Jessica! We are so proud of you.
This abstract was presented today, April 8th at the 2019 Association for Research in Vision and Opthalmology (ARVO) meetings in Vancouver, Canada as a platform presentation by Crystal L. Sigulinsky, Rebecca L. Pfeiffer, James R. Anderson, Daniel P. Emrich, Christopher Rapp, Jeebika Dahal, Jessica Garcia, Hope Morrison, Kevin D. Rapp, Jia-Hui Yang, Carl B. Watt, Robert E. Marc and Bryan W. Jones.
In mouse models of retinal degeneration, connexin36-containing gap junctions in the Aii amacrine cell network appear to mediate aberrant hyperactivity within the retina. However, it remains unclear whether this hyperactivity reflects changes in the underlying circuitry or dysfunction of the normative circuitry. Our connectomics-based mapping of retinal circuitry in rabbit Retinal Connectome 1 (RC1) has dramatically expanded the coupled Aii network. In addition to canonical Aii-to-Aii and Aii-to-ON cone bipolar cell (CBC) coupling, we describe pervasive in- and cross-class coupling motifs among ON CBCs. This study examines the changes in these coupling motifs in RPC1, an ultrastructural retinal pathoconnectome from a rabbit model of retinitis pigmentosa.
RC1 and RPC1 are connectomes built by automated transmission electron microscopy at ultrastructural (2 nm/pixel) resolution. RC1 is a 0.25 mm diameter volume of retina from a 13 month old, light-adapted female Dutch Belted rabbit and serves as the healthy reference connectome. RPC1 is a 0.09 mm diameter volume of pathological retina from a 10 month old, male transgenic P347L model of autosomal dominant retinitis pigmentosa showing early phase 1 retinal remodeling, when rod photoreceptors are still present, but stressed. ON CBCs, Aii amacrine cells, and their coupling partners were annotated using the Viking application. Coupling motifs and features were explored with 3D rendering and graph visualization of connectivity. Gap junctions were validated by 0.25 nm resolution recapture with goniometric tilt when necessary.
All major coupling motifs were observed. Several ON CBC classes retained their class-specific coupling profiles, accepting and rejecting specific combinations of Aii and ON CBC class partnerships. However, aberrant partnerships exist in the coupled network, including both loss of prominent motifs and acquisition of novel ones.
Clearly aberrant morphological and synaptic changes exist in RPC1, including changes in the coupling specificity and gap junction distributions of both Aii amacrine cells and ON CBCs. This indicates that the Aii/ON CBC circuit topology is already altered during early phase 1 remodeling, with substantial implications for therapeutic interventions for blinding diseases that depend upon the surviving retinal network in human patients.
The Marclab is off to ARVO 2019 and eager to share some of what we’ve been up to over the past year. We have undergraduate Jeebika Dahal presenting her work on the AII Amacrine Cell Connectivity Changes In Degenerating Retina on Sunday (see poster B0013 Abstract Number: 551 – B0013). Undergraduate Selena Wirthlin will present her work on the Comparative Anatomy and Connectivity Of The AII Amacrine Cell In Mouse And Rabbit Retina on Sunday (poster B0010 Abstract Number: 548 – B0010). Undergraduate and US Navy veteran Jessica Garcia will present her work Sunday on OFF-layer Branches Of ON Cone Bipolar Cells In Early Retinal Degeneration (B0017 Abstract Number: 555 – B0017). And postdoc Crystal Sigulinsky will present her work on Coupling Architecture Of The Aii/ON Cone Bipolar Cell Network In Degenerate Retina in a platform presentation on Thursday at 11:15am (Abstract Number: 6441).
We hope to see you there!
One of the undergraduates in the lab, Jessica Garcia is seen here annotating conectomes in the lab prior to her presentation at this years ARVO conference. Jessica came to us by way of service with the US Navy, and in our lab is exploring the OFF-layer branches of ON cone bipolar cells in early retinal degeneration. This is important work as we are unraveling how circuitry in the retina changes in neurodegenerative disease.