EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS

Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechan...

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Autores principales: V. V. Neroev, N. V. Balatskaya, E. V. Svetlova, N. V. Neroeva, P. A. Ilyukhin, M. V. Ryabina, A. G. Karmokova
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Publicado: SPb RAACI 2021
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spelling oai:doaj.org-article:63c1b5164ed14d88951a70abc751a3582021-11-18T08:03:51ZEXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS1563-06252313-741X10.15789/1563-0625-ELE-2255https://doaj.org/article/63c1b5164ed14d88951a70abc751a3582021-10-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/2422https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XDegenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies.V. V. NeroevN. V. BalatskayaE. V. SvetlovaN. V. NeroevaP. A. IlyukhinM. V. RyabinaA. G. KarmokovaSPb RAACIarticleamdatrophy of the retinal pigment epitheliumretina-choroid complexproinflammatory cytokinesgene expressionrt-pcrImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 23, Iss 4, Pp 813-818 (2021)
institution DOAJ
collection DOAJ
language RU
topic amd
atrophy of the retinal pigment epithelium
retina-choroid complex
proinflammatory cytokines
gene expression
rt-pcr
Immunologic diseases. Allergy
RC581-607
spellingShingle amd
atrophy of the retinal pigment epithelium
retina-choroid complex
proinflammatory cytokines
gene expression
rt-pcr
Immunologic diseases. Allergy
RC581-607
V. V. Neroev
N. V. Balatskaya
E. V. Svetlova
N. V. Neroeva
P. A. Ilyukhin
M. V. Ryabina
A. G. Karmokova
EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
description Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies.
format article
author V. V. Neroev
N. V. Balatskaya
E. V. Svetlova
N. V. Neroeva
P. A. Ilyukhin
M. V. Ryabina
A. G. Karmokova
author_facet V. V. Neroev
N. V. Balatskaya
E. V. Svetlova
N. V. Neroeva
P. A. Ilyukhin
M. V. Ryabina
A. G. Karmokova
author_sort V. V. Neroev
title EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
title_short EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
title_full EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
title_fullStr EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
title_full_unstemmed EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS
title_sort examining locally expressed mrna of inflammatory mediator genes in a model of retinal pigment epithelium atrophy and retinal degeneration induced by subretinal saline injection in rabbits
publisher SPb RAACI
publishDate 2021
url https://doaj.org/article/63c1b5164ed14d88951a70abc751a358
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