Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response

Connie Y Yeh; Kristin L Koehl; Christine D Harman; Simone Iwabe; José M Guzman; Simon M Petersen-Jones; Randy H Kardon; András M Komáromy

doi:10.1167/iovs.16-19865

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Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response

Journal article

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Peer reviewed

Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response

Connie Y Yeh, Kristin L Koehl, Christine D Harman, Simone Iwabe, José M Guzman, Simon M Petersen-Jones, Randy H Kardon and András M Komáromy

Investigative ophthalmology & visual science, Vol.58(1), pp.65-78

01/01/2017

DOI: 10.1167/iovs.16-19865

PMCID: PMC5231906

PMID: 28061512

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Abstract

The purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs. Chromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry. Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas. Pupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases.

Immunohistochemistry

Retinal Ganglion Cells - physiology

Rod Opsins - biosynthesis

Gene Expression Regulation

Retinal Cone Photoreceptor Cells - physiology

Reverse Transcriptase Polymerase Chain Reaction

RNA - genetics

Reflex, Pupillary - physiology

Retinal Ganglion Cells - cytology

Rod Opsins - genetics

Animals

Retinal Cone Photoreceptor Cells - cytology

Retinal Rod Photoreceptor Cells - cytology

Retinal Rod Photoreceptor Cells - physiology

Dogs

Models, Animal

Microscopy, Acoustic

Photic Stimulation

Details

Title: Subtitle: Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response
Creators: Connie Y Yeh - College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States 2School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Kristin L Koehl - College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States
Christine D Harman - College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States
Simone Iwabe - School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
José M Guzman - School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Simon M Petersen-Jones - College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States
Randy H Kardon - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States 4Veterans Affairs Health Care System, Iowa City, Iowa, United States
András M Komáromy - College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States 2School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.58(1), pp.65-78
DOI: 10.1167/iovs.16-19865
PMID: 28061512
PMCID: PMC5231906
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY006855 / NEI NIH HHS R01 EY017549 / NEI NIH HHS T32 RR007063 / NCRR NIH HHS
Language: English
Date published: 01/01/2017
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979996102771

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