Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visu...

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Main Authors: Marci L. DeRamus, Jessica V. Jasien, Jess M. Eppstein, Pravallika Koala, Timothy W. Kraft
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10655
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author Marci L. DeRamus
Jessica V. Jasien
Jess M. Eppstein
Pravallika Koala
Timothy W. Kraft
author_facet Marci L. DeRamus
Jessica V. Jasien
Jess M. Eppstein
Pravallika Koala
Timothy W. Kraft
author_sort Marci L. DeRamus
collection DOAJ
description Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.
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spelling doaj.art-57a00a55b2a548439320d6b92bbd28b72023-11-18T16:41:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131065510.3390/ijms241310655Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out MiceMarci L. DeRamus0Jessica V. Jasien1Jess M. Eppstein2Pravallika Koala3Timothy W. Kraft4Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USAInterphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.https://www.mdpi.com/1422-0067/24/13/10655IRBPretinaRPEERGOKRflicker
spellingShingle Marci L. DeRamus
Jessica V. Jasien
Jess M. Eppstein
Pravallika Koala
Timothy W. Kraft
Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
International Journal of Molecular Sciences
IRBP
retina
RPE
ERG
OKR
flicker
title Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
title_full Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
title_fullStr Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
title_full_unstemmed Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
title_short Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice
title_sort retinal responses to visual stimuli in interphotoreceptor retinoid binding protein knock out mice
topic IRBP
retina
RPE
ERG
OKR
flicker
url https://www.mdpi.com/1422-0067/24/13/10655
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