The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely...

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Main Authors: Serena Riccitelli, Mattia Di Paolo, James Ashley, Silvia Bisti, Stefano Di Marco
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/6/1561
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author Serena Riccitelli
Mattia Di Paolo
James Ashley
Silvia Bisti
Stefano Di Marco
author_facet Serena Riccitelli
Mattia Di Paolo
James Ashley
Silvia Bisti
Stefano Di Marco
author_sort Serena Riccitelli
collection DOAJ
description Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.
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spelling doaj.art-4eaed2635511478fb30d9b259008e8ed2023-11-22T01:00:46ZengMDPI AGCells2073-44092021-06-01106156110.3390/cells10061561The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat RetinasSerena Riccitelli0Mattia Di Paolo1James Ashley2Silvia Bisti3Stefano Di Marco4Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, ItalySchool of Biological Sciences, The University of Manchester, Manchester M13 9PL, UKDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, ItalyRetinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.https://www.mdpi.com/2073-4409/10/6/1561light damageneurodegenerationfunctional analysisearly detectionremodeling
spellingShingle Serena Riccitelli
Mattia Di Paolo
James Ashley
Silvia Bisti
Stefano Di Marco
The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
Cells
light damage
neurodegeneration
functional analysis
early detection
remodeling
title The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
title_full The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
title_fullStr The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
title_full_unstemmed The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
title_short The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas
title_sort timecourses of functional morphological and molecular changes triggered by light exposure in sprague dawley rat retinas
topic light damage
neurodegeneration
functional analysis
early detection
remodeling
url https://www.mdpi.com/2073-4409/10/6/1561
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