The role of the mTOR pathway in diabetic retinopathy

Abstract

The retina, the part of the eye, translates the light signal into an electric current that can be sent to the brain as visual information. To achieve this, the retina requires fine-tuned vascularization for its energy supply. Diabetic retinopathy (DR) causes alterations in the eye vascularization that reduce the oxygen supply with consequent retinal neurodegeneration. During DR, the mammalian target of rapamycin (mTOR) pathway seems to coordinate retinal neurodegeneration with multiple anabolic and catabolic processes, such as autophagy, oxidative stress, cell death, and the release of pro-inflammatory cytokines, which are closely related to chronic hyperglycemia. This review outlines the normal anatomy of the retina and how hyperglycemia can be involved in the neurodegeneration underlying this disease through over activation or inhibition of the mTOR pathway.

Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis

“…To identify changes in autophagy levels in DR, we assessed changes in expression of autophagy-associated proteins and found that the expression of LC3II/I and Beclin1 in HG-induced ARPE-19 cells was significantly downregulated, whereas the expression of p62 was significantly upregulated, indicating that high glucose inhibited autophagy. As mTOR affects the progression of DR (Casciano et al 2022 ) and Sestrin2 has been implicated in induction of autophagy under stress conditions by inhibiting mTOR (Kim et al 2015 ; Kim and Guan 2015 ), we examined the effects of activating the mTOR pathway on cells over-expressing Sestrin2. Treating ARPE-19 cells with MHY1458, which activates mTOR pathway reversed the protective effects of Sestrin2 over-expression.…”

Microglia-endothelial cross-talk regulates diabetes-induced retinal vascular dysfunction through remodeling inflammatory microenvironment

“…The upregulation of mTOR activity is likely attributed to elevated circulating levels of insulin, amino acids, and proinflammatory cytokines, indicative of the early endothelial cell injury. 23 Specifically, we observed that EC-C0 contained a higher proportion of functional genes associated with cell migration, cell proliferation, blood vessel development, and angiogenesis ( Figure 3 D). The KEGG pathway analysis demonstrated a strong activation of vascular development and induction of inflammation-related pathways, such as the TNF signaling pathway, FoxO signaling pathway, Rap1 signaling pathway, and Hippo signaling pathway, in the EC-C0 ( Figure 3 E).…”

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

“…Autophagy processes can recycle cytoplasmic organelles and components for eventual tissue remodeling [37,69,86,87,175,177,[207][208][209][210][211][212][213][214][215][216]. There are subtypes of autophagy processing.…”

“…The mechanistic target of rapamycin (mTOR) is a 289-kDa serine/threonine protein kinase that is encoded by a single gene FRAP1 [6,81,87,212,[246][247][248][249]. mTOR also is known as the mammalian target of rapamycin and the FK506-binding protein 12-rapamycin complex-associated protein 1 [222].…”

“…Long-COVID, also known as long-haul COVID, post-acute COVID-19, and chronic COVID, represents long-term effects that can occur following acute SARS-CoV-2 infection. Multiple mechanisms can account for this chronic syndrome, including metabolic pathways, apoptosis, autophagy, oxidative stress, mitochondrial dysfunction, and cytokine release [56,73,74,[86][87][88]91,177,178,180,206,212,251,[385][386][387][388][389][390][391][392][393]. With the knowledge of the role of APOE-ε4 in metabolism and autophagy signaling, APOE-ε4 has been linked to the effects of long COVID and dementia.…”