• PNAS Front Matter Portal
  • Science Sessions: The PNAS Podcast Program

Imaging and quantifying ganglion cells and other transparent neurons in the living human retina

  1. Donald T. Millera
  1. aSchool of Optometry, Indiana University, Bloomington, IN 47405;
  2. bPurdue School of Engineering and Technology, Indiana University–Purdue University Indianapolis, Indianapolis, IN 46202
  1. Edited by David R. Williams, University of Rochester, Rochester, NY, and approved October 18, 2017 (received for review June 30, 2017)


Ganglion cells are the primary building block of retinal neural circuitry, but have been elusive to observe and quantify in the living human eye. Here, we show a light microscopy modality that reveals not only the somas of these cells, but also their 3D packing geometry, primary subtypes, and spatial projection to other neurons. The method provides a glimpse of the rich tapestry of neurons, glia, and blood vessels that compose the retina, thus exposing the anatomical substrate for neural processing of visual information. Clinically, high-resolution images of retinal neurons in living eyes hold promise for improved diagnosis and assessing treatment of ganglion cell and other neuron loss in retinal disease.


Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency. Failure of conventional imaging—using predominately singly scattered light—to reveal GCs has led to a focus on multiply-scattered, fluorescence, two-photon, and phase imaging techniques to enhance GC contrast. Here, we show that singly scattered light actually carries substantial information that reveals GC somas, axons, and other retinal neurons and permits their quantitative analysis. We perform morphometry on GC layer somas, including projection of GCs onto photoreceptors and identification of the primary GC subtypes, even beneath nerve fibers. We obtained singly scattered images by: (i) marrying adaptive optics to optical coherence tomography to avoid optical blurring of the eye; (ii) performing 3D subcellular image registration to avoid motion blur; and (iii) using organelle motility inside somas as an intrinsic contrast agent. Moreover, through-focus imaging offers the potential to spatially map individual GCs to underlying amacrine, bipolar, horizontal, photoreceptor, and retinal pigment epithelium cells, thus exposing the anatomical substrate for neural processing of visual information. This imaging modality is also a tool for improving clinical diagnosis and assessing treatment of retinal disease.


  • ?1To whom correspondence should be addressed. Email: liuzhuo{at}indiana.edu.
  • Author contributions: Z.L. and D.T.M. conceived and designed the project; Z.L., K.K., and J.J.L. developed image reconstruction, processing, and registration tools; Z.L. contributed new analytic tools, Z.L., K.K., and F.Z. performed the experiments, Z.L., K.K., F.Z., and D.T.M. analyzed the results; Z.L. and D.T.M. wrote the paper and all authors contributed to revisions; and D.T.M. supervised the project.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1711734114/-/DCSupplemental.

Online Impact

    <var id="UPyyYwe"><strike id="UPyyYwe"></strike></var>
    <ins id="UPyyYwe"></ins>
    <ins id="UPyyYwe"></ins>
    <cite id="UPyyYwe"><video id="UPyyYwe"></video></cite>
    <ins id="UPyyYwe"></ins><ins id="UPyyYwe"><span id="UPyyYwe"><cite id="UPyyYwe"></cite></span></ins>
    <var id="UPyyYwe"><span id="UPyyYwe"></span></var>
    <cite id="UPyyYwe"><video id="UPyyYwe"><var id="UPyyYwe"></var></video></cite>
    <cite id="UPyyYwe"></cite>
    <var id="UPyyYwe"></var>
    <cite id="UPyyYwe"></cite>
    <ins id="UPyyYwe"></ins>
    <cite id="UPyyYwe"><span id="UPyyYwe"></span></cite><cite id="UPyyYwe"></cite>
    <var id="UPyyYwe"><video id="UPyyYwe"><menuitem id="UPyyYwe"></menuitem></video></var>
    <var id="UPyyYwe"><span id="UPyyYwe"></span></var>
    <ins id="UPyyYwe"></ins>
    <ins id="UPyyYwe"></ins><var id="UPyyYwe"><span id="UPyyYwe"></span></var>
    <var id="UPyyYwe"><span id="UPyyYwe"></span></var>
    <cite id="UPyyYwe"></cite>
    <var id="UPyyYwe"><strike id="UPyyYwe"><menuitem id="UPyyYwe"></menuitem></strike></var>
    <ins id="UPyyYwe"></ins>
    <cite id="UPyyYwe"></cite><cite id="UPyyYwe"></cite>
  • 8686301327 2018-02-22
  • 1879481326 2018-02-22
  • 9332351325 2018-02-22
  • 7384141324 2018-02-22
  • 8918371323 2018-02-22
  • 7638311322 2018-02-22
  • 9654151321 2018-02-22
  • 1588961320 2018-02-22
  • 5712971319 2018-02-22
  • 5536211318 2018-02-22
  • 4417061317 2018-02-22
  • 3024201316 2018-02-21
  • 4658931315 2018-02-21
  • 3216561314 2018-02-21
  • 1965251313 2018-02-21
  • 970811312 2018-02-21
  • 609011311 2018-02-21
  • 3219131310 2018-02-21
  • 613261309 2018-02-21
  • 6972481308 2018-02-21