mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration

Age-associated decline in retina function is largely responsible for the irreversible vision deterioration in the elderly population. It is also an important risk factor for the development of degenerative and angiogenic diseases. However, the molecular mechanisms involved in the process of aging in...

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Autores principales:	Yu-Qing Rao, Yu-Tong Zhou, Wenchuan Zhou, Jia-Kai Li, Baojie Li, Jing Li
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/f9d7269548704e2984ceaec4993e62bd
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spelling	oai:doaj.org-article:f9d7269548704e2984ceaec4993e62bd2021-11-15T01:20:03ZmTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration1942-099410.1155/2021/6715758https://doaj.org/article/f9d7269548704e2984ceaec4993e62bd2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6715758https://doaj.org/toc/1942-0994Age-associated decline in retina function is largely responsible for the irreversible vision deterioration in the elderly population. It is also an important risk factor for the development of degenerative and angiogenic diseases. However, the molecular mechanisms involved in the process of aging in the retina remain largely elusive. This study investigated the role of mTORC1 signaling in aging of the retina. We showed that mTORC1 was activated in old-aged retina, particularly in the ganglion cells. The role of mTORC1 activation was further investigated in Chx10-Cre;Tsc1fx/fx mouse (Tsc1-cKO). Activation of mTORC1 was found in bipolar and some of the ganglion and amacrine cells in the adult Tsc1-cKO retina. Bipolar cell hypertrophy and Müller gliosis were observed in Tsc1-cKO since 6 weeks of age. The abnormal endings of bipolar cell dendritic tips at the outer nuclear layer resembled that of the old-aged mice. Microglial cell activation became evident in 6-week-old Tsc1-cKO. At 5 months, the Tsc1-cKO mice exhibited advanced features of old-aged retina, including the expression of p16Ink4a and p21, expression of SA-β-gal in ganglion cells, decreased photoreceptor cell numbers, decreased electroretinogram responses, increased oxidative stress, microglial cell activation, and increased expression of immune and inflammatory genes. Inhibition of microglial cells by minocycline partially prevented photoreceptor cell loss and restored the electroretinogram responses. Collectively, our study showed that the activation of mTORC1 signaling accelerated aging of the retina by both cell autonomous and nonautonomous mechanisms. Our study also highlighted the role of microglia cells in driving the decline in retina function.Yu-Qing RaoYu-Tong ZhouWenchuan ZhouJia-Kai LiBaojie LiJing LiHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Yu-Qing Rao Yu-Tong Zhou Wenchuan Zhou Jia-Kai Li Baojie Li Jing Li mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
description	Age-associated decline in retina function is largely responsible for the irreversible vision deterioration in the elderly population. It is also an important risk factor for the development of degenerative and angiogenic diseases. However, the molecular mechanisms involved in the process of aging in the retina remain largely elusive. This study investigated the role of mTORC1 signaling in aging of the retina. We showed that mTORC1 was activated in old-aged retina, particularly in the ganglion cells. The role of mTORC1 activation was further investigated in Chx10-Cre;Tsc1fx/fx mouse (Tsc1-cKO). Activation of mTORC1 was found in bipolar and some of the ganglion and amacrine cells in the adult Tsc1-cKO retina. Bipolar cell hypertrophy and Müller gliosis were observed in Tsc1-cKO since 6 weeks of age. The abnormal endings of bipolar cell dendritic tips at the outer nuclear layer resembled that of the old-aged mice. Microglial cell activation became evident in 6-week-old Tsc1-cKO. At 5 months, the Tsc1-cKO mice exhibited advanced features of old-aged retina, including the expression of p16Ink4a and p21, expression of SA-β-gal in ganglion cells, decreased photoreceptor cell numbers, decreased electroretinogram responses, increased oxidative stress, microglial cell activation, and increased expression of immune and inflammatory genes. Inhibition of microglial cells by minocycline partially prevented photoreceptor cell loss and restored the electroretinogram responses. Collectively, our study showed that the activation of mTORC1 signaling accelerated aging of the retina by both cell autonomous and nonautonomous mechanisms. Our study also highlighted the role of microglia cells in driving the decline in retina function.
format	article
author	Yu-Qing Rao Yu-Tong Zhou Wenchuan Zhou Jia-Kai Li Baojie Li Jing Li
author_facet	Yu-Qing Rao Yu-Tong Zhou Wenchuan Zhou Jia-Kai Li Baojie Li Jing Li
author_sort	Yu-Qing Rao
title	mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
title_short	mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
title_full	mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
title_fullStr	mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
title_full_unstemmed	mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
title_sort	mtorc1 activation in chx10-specific tsc1 knockout mice accelerates retina aging and degeneration
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/f9d7269548704e2984ceaec4993e62bd
work_keys_str_mv	AT yuqingrao mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration AT yutongzhou mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration AT wenchuanzhou mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration AT jiakaili mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration AT baojieli mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration AT jingli mtorc1activationinchx10specifictsc1knockoutmiceacceleratesretinaaginganddegeneration
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mTORC1 Activation in Chx10-Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration

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