1Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea, 2Integrative Research Support Centre, College of Medicine,The Catholic University of Korea, Seoul, Korea, 3Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea, 4Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea, 5Department of Ophthalmology and Visual Sciences, University of Texas Health Services Centre, Texas, United States of America

The eye creates our visual impression of the world. The eye’s retina converts light signals into electrical signals, processes them and transmits them to the brain. Yet, despite the retina’s importance, the complex relationship between its anatomy and physiology is not yet fully understood. Part of the reason might be that characterizing the retina requires an imaging and analysis technique that’s able to capture details only several dozen nanometers in size. In this study, the Mimics® Innovation Suite helped Kim et al. use immuno-electron microscopy to characterize a new visual processing pathway.

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Figure 2

New Retinal Processing Pathway

Kim et al. were interested in the functional relationship between the retina’s anatomy and physiology that determines its computational power. Prior to their study, researchers discovered a new processing pathway that violated a key principle of retinal organization. Following this discovery, the team wanted to find out how the neural synapses (the interfaces between neurons) differ for this new pathway.

How to Analyze Anatomy at the Nanoscale?

The key challenges in imaging neurons – or any other biological matter – are size and functional selectivity. The synaptic features Kim et al. planned to observe measure only several dozen nanometers in size. In addition, because “functional selectivity” requires visually identifying different types of neurons, the imaging technique must have superior resolution and contrast. The team chose to employ immuno-electron microscopy.

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Figure 3

Configuration of Neural Synapses Depends on Anatomy

Figure 2 shows a thin section of a rabbit’s retina taken with immuno-electron microscopy. Each section is 70 – 90 nm thick and has undergone immunocytochemical treatment to ensure good conductibility and contrast. The researchers imaged an average of 36 sections individually and reoriented them to form an image stack. This image stack was masked, imported into the Mimics® Innovation Suite and, as shown in Figure 3, converted into a 3D reconstruction.

Figure 2 shows a thin section of a rabbit’s retina taken with immuno-electron microscopy. Each section is 70 – 90 nm thick and has undergone immunocytochemical treatment to ensure good conductibility and contrast. The researchers imaged an average of 36 sections individually and reoriented them to form an image stack. This image stack was masked, imported into the Mimics® Innovation Suite and, as shown in Figure 3, converted into a 3D reconstruction.

The 3D model shows a type of neuron called the “ON cone bipolar cell”. Historically, the ON cone bipolar cell was believed to form a synapse with other neural cells only at a specific location, namely at the ON layer or sublamina b. This was considered to be a key principle of the retina. However, Kim et al. confirmed previous studies showing that certain ON cone bipolar cells violate this key principle by also forming a synapse in a different location, the so-called OFF layer or sublamina a. The arrows in Figure 2 mark two synaptic ribbons of an ON cone bipolar cell within the OFF layer.

 

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Figure 4

 

Characterizing the synapses of an ON cone bipolar cell at the two different locations – the ON and OFF layers – was the main focus of the team’s study. Figure 4 shows the synaptic ribbons in the ON and OFF layers as extracted from the 3D reconstruction in Figure 3. Their distinctively different configurations are clearly visible. The researchers also succeeded in quantifying their physical nanoscale dimensions based on the 3D model.

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The Standard in ‘Engineering on AnatomyTM

The Mimics Innovation Suite turns 3D image data into high-quality digital models. Starting from CT, MRI or 3D ultrasound images, the Mimics®  Innovation Suite offers the most advanced image segmentation, the broadest anatomical measurement options, powerful CAD tools for Engineering on Anatomy and 3D Printing, and accurate model preparation for FEA and CFD. The authors used the Mimics®  Innovation Suite to characterize the synapses of single neurons using the following steps:

  • Convert electron microscopy images into an accurate 3D reconstruction
  • Visualize the functional relation between different neurons and synapses
  • Verify the accuracy of the slicing process
  • Calculate and compare the synaptic efficiencies