All Publications


  • Cryogenic electron tomography and elemental analysis of mitochondrial granules in human retinal ganglion cells. Structure (London, England : 1993) Wu, G. H., Hou, C., Thron, A., Patel, H. R., Spillane, L., Gupte, S. R., Yeung-Levy, S., Gulati, S., Booth, C., Liao, Y. J., Chiu, W. 2025

    Abstract

    Combining three-dimensional (3D) visualization with elemental analysis of vitrified cells can provide crucial insights into subcellular structures and elemental compositions in their native environments. We present a coordinated approach using cryogenic electron energy loss spectroscopy (cryoEELS) and cryogenic electron tomography (cryoET) to characterize the elemental distribution and ultrastructure of vitrified cells. We applied this method to examine calcium disposition in the mitochondria of cultured human retinal ganglion cells (RGCs) exposed to pro-calcifying conditions relevant to optic disc drusen pathology. Our cryoEELS analysis revealed mitochondrial granules with elevated calcium signals, offering direct evidence of mitochondrial calcification. Additionally, cryoET coupled with artificial intelligence-based analysis enabled quantification of the volume and spatial distribution of these calcium granules. This integrated workflow can be broadly applied to various cell types, facilitating the study of ultrastructure and elemental distribution in subcellular structures under diverse physiological and pathological conditions, as well as in response to therapeutic interventions.

    View details for DOI 10.1016/j.str.2025.07.010

    View details for PubMedID 40763734

  • Chemical induction of neurogenic properties in mammalian Müller glia. Stem cells (Dayton, Ohio) Xia, X., Teotia, P., Patel, H., Van Hook, M. J., Ahmad, I. 2021; 39 (8): 1081-1090

    Abstract

    Müller glia (MG), cells that maintain homeostasis in the retina, are dormant stem cells that can regenerate neurons upon injury. However, the regenerative property of MG, which is reproducibly displayed in the lower vertebrates, is not readily observed in the mammals even upon forced expression of regulatory genes or exposure to growth factors. Here, we demonstrate a reproducible unmasking of the neurogenic properties of enriched rodent MG by serial exposure to different combinations of small molecules. The enriched MG, in response to changing culture conditions, silenced glia-specific genes and acquired transcriptional signature of neurons, accompanied by upregulation of genes known to regulate neuronal potential of MG. The MG-derived neurons expressed immunoreactivities corresponding to neuronal proteins and displayed electrophysiological features of immature neurons. Our study presents a proof of principle of pharmacological activation of neurogenic properties of mammalian MG, which may be utilized for therapeutic regeneration.

    View details for DOI 10.1002/stem.3370

    View details for PubMedID 33764634