p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model
Kolosova N. G., Kozhevnikova O. S., Telegina D. V., Fursova A. Z., Stefanova N. A., Muraleva N. A., Venantsi F., Sherman M. Y., Kolesnikov S. I., Sufianov A. A., Gabai V. L., Shnejder A. M.
Aging-US
Vol.10, Issue8, P. 2136-2147
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.18632/aging.101537
Аннотация:
P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1- encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an agerelated macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats, as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina
Ключевые слова:
Age-related macular degeneration; Aging; Gliosis; Inflammation; OXYS rats; p62/SQSTM1; Retina
DNA; sequestosome 1; Sqstm1 protein, rat; aging; animal; gene expression regulation; gene therapy; genetics; human; inbred rat strain; macular degeneration; male; metabolism; plasmid; rat; Aging; Animals; DNA; Gene Expression Regulation; Genetic Therapy; Humans; Macular Degeneration; Male; Plasmids; Rats; Rats, Inbred Strains; Sequestosome-1 Protein
Язык текста: Английский
ISSN: 1945-4589
Kolosova N. G.
Kozhevnikova O. S.
Telegina D. V.
Fursova A. Z.
Stefanova N. A.
Muraleva N. A.
Venantsi F. Franko 1951-
Sherman M. Y.
Kolesnikov S. I.
Sufianov A. A. Al`bert Akramovich 1965-
Gabai V. L.
Shnejder A. M. Aleksandr M 1968-
Колосова Н. Г.
Кожевникова О. С.
Телегина Д. В.
Фурсова А. З.
Стефанова Н. А.
Муралева Н. А.
Венанци Ф. Франко 1951-
Шерман М. Y.
Колесников С. И.
Суфианов А. А. Альберт Акрамович 1965-
Габаи В. Л.
Шнейдер А. М. Александр М 1968-
p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model
Текст визуальный непосредственный
Aging-US
Vol.10, Issue8 P. 2136-2147
2018
Статья
Age-related macular degeneration Aging Gliosis Inflammation OXYS rats p62/SQSTM1 Retina
DNA sequestosome 1 Sqstm1 protein, rat aging animal gene expression regulation gene therapy genetics human inbred rat strain macular degeneration male metabolism plasmid rat Aging Animals DNA Gene Expression Regulation Genetic Therapy Humans Macular Degeneration Male Plasmids Rats Rats, Inbred Strains Sequestosome-1 Protein
P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1- encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an agerelated macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats, as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina