Molecular And Spatial Analysis Of Ganglion Cells Onretinal Flatmounts Identifies Perivascular Neuronsresilient To Glaucoma Kushal Nimkar Nicole Y Tsai Mengya Zhao Yujuan Yi Matthew R Lum Tavita R Garrett Yixiao Wang Kenichi Toma Franklin Cavalholme Nikhil Reddy Aliza T Ehrlich Arnold R Kriegstein Michael Tri H Do Yang Hu Benjamin Sivyer by Kushal Nimkar & Nicole Y. Tsai & Mengya Zhao & Yujuan Yi & Matthew R. Lum & Tavita R. Garrett & Yixiao Wang & Kenichi Toma & Franklin Caval-holme & Nikhil Reddy & Aliza T. Ehrlich & Arnold R. Kriegstein & Michael Tri H. Do & Yang Hu & Benjamin Sivyer &... instant download after payment.

SUMMARYRecent transcriptomic studies have categorized mouse retinal ganglion cells (RGCs) into 45 types; however,little is known about their spatial distributions on the two-dimensional retinal surface and how their local microenvironments impact their functions. Here, we optimized a workflow combining imaging-based spatialtranscriptomics (multiplexed-error robust fluorescent in situ hybridization [MERFISH]) and immunostainingon retinal flatmounts. We computationally registered the somata distributions of all RGCs and found that34/45 molecularly defined types exhibited non-uniform distributions. We analyzed local neighborhoods foreach cell and identified seven RGC types enriched in the perivascular niche, including direction-selectiveRGC (DSGC) and intrinsically photosensitive RGC (ipRGC) types. We further examined an experimental glaucoma model and found that surviving RGCs are enriched in the perivascular niche. Perivascular DSGCs andM1 ipRGCs were especially resilient, suggesting that proximity to vasculatures confers mTOR-independent,cell-extrinsic neuroprotection. Together, our work provides a comprehensive spatial atlas of RGC types andlinks their microenvironment to differential vulnerability in neurodegeneration.