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      In vivo Morphometry of Inner Plexiform Layer (IPL) Stratification in the Human Retina With Visible Light Optical Coherence Tomography

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          Abstract

          From the bipolar cells to higher brain visual centers, signals in the vertebrate visual system are transmitted along parallel on and off pathways. These two pathways are spatially segregated along the depth axis of the retina. Yet, to our knowledge, there is no way to directly assess this anatomical stratification in vivo. Here, employing ultrahigh resolution visible light Optical Coherence Tomography (OCT) imaging in humans, we report a stereotyped reflectivity pattern of the inner plexiform layer (IPL) that parallels IPL stratification. We characterize the topography of this reflectivity pattern non-invasively in a cohort of normal, young adult human subjects. This proposed correlate of IPL stratification is accessible through non-invasive ocular imaging in living humans. Topographic variations should be carefully considered when designing studies in development or diseases of the visual system.

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          Most cited references39

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          Optical coherence tomography.

          A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.
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            Glaucomatous damage of the macula.

            There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Parallel processing in the mammalian retina.

              Our eyes send different 'images' of the outside world to the brain - an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer - the inner plexiform layer - circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                29 April 2021
                2021
                : 15
                : 655096
                Affiliations
                [1] 1Department of Biomedical Engineering, University of California , Davis, Davis, CA, United States
                [2] 2Department of Ophthalmology and Vision Science, School of Medicine, University of California , Davis, Sacramento, CA, United States
                [3] 3Department of Ophthalmology, NYU Langone Health , New York, NY, United States
                [4] 4Department of Radiology, NYU Langone Health , New York, NY, United States
                [5] 5Tech4Health Institute, NYU Langone Health , New York, NY, United States
                Author notes

                Edited by: Tamas Kovács-Öller, University of Pécs, Hungary

                Reviewed by: Michael Dietrich, University Hospital of Düsseldorf, Germany; Wu Yuan, The Chinese University of Hong Kong, China; Bernardes Rui, University of Coimbra, Portugal

                *Correspondence: Vivek J. Srinivasan, vjsriniv@ 123456ucdavis.edu

                This article was submitted to Cellular Neurophysiology, a section of the journal Frontiers in Cellular Neuroscience

                Article
                10.3389/fncel.2021.655096
                8118202
                33994948
                0d73adf4-e73a-44f1-89a4-16e29429a7f7
                Copyright © 2021 Zhang, Kho and Srinivasan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 January 2021
                : 07 April 2021
                Page count
                Figures: 10, Tables: 2, Equations: 0, References: 39, Pages: 13, Words: 0
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: NS094681
                Award ID: EB029747
                Award ID: EB023591
                Award ID: EY026556
                Award ID: EY028287
                Award ID: EY015387
                Award ID: EY031469
                Award ID: EY012576
                Categories
                Cellular Neuroscience
                Original Research

                Neurosciences
                retina,inner plexiform layer,outer plexiform layer,retinal lamination,synapses,visible light optical coherence tomography,bipolar cells,ganglion cells

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