Activation of sigma 1 receptor extends survival of cones and improves visual acuity in a murine model of retinitis pigmentosa

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Abstract

PURPOSE. Retinitis pigmentosa (RP), a retinal photoreceptor degeneration, typically affects rod function and subsequently cones. Activation of sigma 1 receptor (Sig1R) has been shown to preserve cone function through 6 weeks in the rd10 mouse model of RP, when mice were treated systemically with the Sig1R ligand (þ)-pentazocine (PTZ). This study determined the extent to which cone function is preserved in rd10 mice when Sig1R is activated. METHODS. Rd10 mice were administered (þ)-PTZ (alternate days beginning at postnatal day [P]14) over a period of 180 days. Mouse visual function and structure were measured in vivo using optokinetic tracking response, scotopic and photopic electroretinography plus photopic assessment using ‘‘natural’’ noise stimuli, and optical coherence tomography (OCT). Immunofluorescent methods were used to detect cones in retinal cryosections. RESULTS. Visual acuity was maintained in rd10(þ)-PTZ-treated mice through P56, whereas rd10 nontreated mice showed marked decline by P28. Cone responses were detected in (þ)PTZ-treated mice through P60, which were more robust when tested with natural noise stimuli; cone responses were minimal in nontreated rd10 mice. OCT revealed significantly thicker retinas in (þ)-PTZ-treated rd10 mice through P60 compared to nontreated mice. Cones were detected by immunofluorescence in (þ)-PTZ-treated rd10 retinas through P120. CONCLUSIONS. The extent to which cone rescue could be sustained in (þ)-PTZ-treated rd10 mice was evaluated comprehensively, showing that activation of Sig1R is associated with prolonged visual acuity, extended detection of cone function, and detection of cones in retinal histologic sections. The data reflect promising long-term neuroprotection when Sig1R is activated.

Original languageEnglish (US)
Pages (from-to)4397-4407
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume60
Issue number13
DOIs
StatePublished - Jan 1 2019

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Retinitis Pigmentosa
Visual Acuity
Pentazocine
Retinal Cone Photoreceptor Cells
Optical Coherence Tomography
Noise
Retina
sigma-1 receptor
Electroretinography
Retinal Degeneration
Vertebrate Photoreceptor Cells
Fluorescent Antibody Technique

Keywords

  • ERG
  • Mouse
  • OCT
  • Pentazocine
  • Retina
  • Retinal degeneration
  • Visual acuity

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{6d3b9fb886444db9a06a18e4ef1440bc,
title = "Activation of sigma 1 receptor extends survival of cones and improves visual acuity in a murine model of retinitis pigmentosa",
abstract = "PURPOSE. Retinitis pigmentosa (RP), a retinal photoreceptor degeneration, typically affects rod function and subsequently cones. Activation of sigma 1 receptor (Sig1R) has been shown to preserve cone function through 6 weeks in the rd10 mouse model of RP, when mice were treated systemically with the Sig1R ligand ({\th})-pentazocine (PTZ). This study determined the extent to which cone function is preserved in rd10 mice when Sig1R is activated. METHODS. Rd10 mice were administered ({\th})-PTZ (alternate days beginning at postnatal day [P]14) over a period of 180 days. Mouse visual function and structure were measured in vivo using optokinetic tracking response, scotopic and photopic electroretinography plus photopic assessment using ‘‘natural’’ noise stimuli, and optical coherence tomography (OCT). Immunofluorescent methods were used to detect cones in retinal cryosections. RESULTS. Visual acuity was maintained in rd10({\th})-PTZ-treated mice through P56, whereas rd10 nontreated mice showed marked decline by P28. Cone responses were detected in ({\th})PTZ-treated mice through P60, which were more robust when tested with natural noise stimuli; cone responses were minimal in nontreated rd10 mice. OCT revealed significantly thicker retinas in ({\th})-PTZ-treated rd10 mice through P60 compared to nontreated mice. Cones were detected by immunofluorescence in ({\th})-PTZ-treated rd10 retinas through P120. CONCLUSIONS. The extent to which cone rescue could be sustained in ({\th})-PTZ-treated rd10 mice was evaluated comprehensively, showing that activation of Sig1R is associated with prolonged visual acuity, extended detection of cone function, and detection of cones in retinal histologic sections. The data reflect promising long-term neuroprotection when Sig1R is activated.",
keywords = "ERG, Mouse, OCT, Pentazocine, Retina, Retinal degeneration, Visual acuity",
author = "Jing Wang and Alan Saul and Smith, {Sylvia B.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1167/iovs.19-27709",
language = "English (US)",
volume = "60",
pages = "4397--4407",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "13",

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TY - JOUR

T1 - Activation of sigma 1 receptor extends survival of cones and improves visual acuity in a murine model of retinitis pigmentosa

AU - Wang, Jing

AU - Saul, Alan

AU - Smith, Sylvia B.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - PURPOSE. Retinitis pigmentosa (RP), a retinal photoreceptor degeneration, typically affects rod function and subsequently cones. Activation of sigma 1 receptor (Sig1R) has been shown to preserve cone function through 6 weeks in the rd10 mouse model of RP, when mice were treated systemically with the Sig1R ligand (þ)-pentazocine (PTZ). This study determined the extent to which cone function is preserved in rd10 mice when Sig1R is activated. METHODS. Rd10 mice were administered (þ)-PTZ (alternate days beginning at postnatal day [P]14) over a period of 180 days. Mouse visual function and structure were measured in vivo using optokinetic tracking response, scotopic and photopic electroretinography plus photopic assessment using ‘‘natural’’ noise stimuli, and optical coherence tomography (OCT). Immunofluorescent methods were used to detect cones in retinal cryosections. RESULTS. Visual acuity was maintained in rd10(þ)-PTZ-treated mice through P56, whereas rd10 nontreated mice showed marked decline by P28. Cone responses were detected in (þ)PTZ-treated mice through P60, which were more robust when tested with natural noise stimuli; cone responses were minimal in nontreated rd10 mice. OCT revealed significantly thicker retinas in (þ)-PTZ-treated rd10 mice through P60 compared to nontreated mice. Cones were detected by immunofluorescence in (þ)-PTZ-treated rd10 retinas through P120. CONCLUSIONS. The extent to which cone rescue could be sustained in (þ)-PTZ-treated rd10 mice was evaluated comprehensively, showing that activation of Sig1R is associated with prolonged visual acuity, extended detection of cone function, and detection of cones in retinal histologic sections. The data reflect promising long-term neuroprotection when Sig1R is activated.

AB - PURPOSE. Retinitis pigmentosa (RP), a retinal photoreceptor degeneration, typically affects rod function and subsequently cones. Activation of sigma 1 receptor (Sig1R) has been shown to preserve cone function through 6 weeks in the rd10 mouse model of RP, when mice were treated systemically with the Sig1R ligand (þ)-pentazocine (PTZ). This study determined the extent to which cone function is preserved in rd10 mice when Sig1R is activated. METHODS. Rd10 mice were administered (þ)-PTZ (alternate days beginning at postnatal day [P]14) over a period of 180 days. Mouse visual function and structure were measured in vivo using optokinetic tracking response, scotopic and photopic electroretinography plus photopic assessment using ‘‘natural’’ noise stimuli, and optical coherence tomography (OCT). Immunofluorescent methods were used to detect cones in retinal cryosections. RESULTS. Visual acuity was maintained in rd10(þ)-PTZ-treated mice through P56, whereas rd10 nontreated mice showed marked decline by P28. Cone responses were detected in (þ)PTZ-treated mice through P60, which were more robust when tested with natural noise stimuli; cone responses were minimal in nontreated rd10 mice. OCT revealed significantly thicker retinas in (þ)-PTZ-treated rd10 mice through P60 compared to nontreated mice. Cones were detected by immunofluorescence in (þ)-PTZ-treated rd10 retinas through P120. CONCLUSIONS. The extent to which cone rescue could be sustained in (þ)-PTZ-treated rd10 mice was evaluated comprehensively, showing that activation of Sig1R is associated with prolonged visual acuity, extended detection of cone function, and detection of cones in retinal histologic sections. The data reflect promising long-term neuroprotection when Sig1R is activated.

KW - ERG

KW - Mouse

KW - OCT

KW - Pentazocine

KW - Retina

KW - Retinal degeneration

KW - Visual acuity

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U2 - 10.1167/iovs.19-27709

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