mTOR Signalling Pathway: A Potential Therapeutic Target for Ocular Neurodegenerative Diseases

Abstract

Recent advances in the research of the mammalian target of the rapamycin (mTOR) signalling pathway demonstrated that mTOR is a robust therapeutic target for ocular degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Although the exact mechanisms of individual ocular degenerative diseases are unclear, they share several common pathological processes, increased and prolonged oxidative stress in particular, which leads to functional and morphological impairment in photoreceptors, retinal ganglion cells (RGCs), or retinal pigment epithelium (RPE). mTOR not only modulates oxidative stress but is also affected by reactive oxygen species (ROS) activation. It is essential to understand the complicated relationship between the mTOR pathway and oxidative stress before its application in the treatment of retinal degeneration. Indeed, the substantial role of mTOR-mediated autophagy in the pathogenies of ocular degenerative diseases should be noted. In reviewing the latest studies, this article summarised the application of rapamycin, an mTOR signalling pathway inhibitor, in different retinal disease models, providing insight into the mechanism of rapamycin in the treatment of retinal neurodegeneration under oxidative stress. Besides basic research, this review also summarised and updated the results of the latest clinical trials of rapamycin in ocular neurodegenerative diseases. In combining the current basic and clinical research results, we provided a more complete picture of mTOR as a potential therapeutic target for ocular neurodegenerative diseases.

m6A-Mediated Upregulation of Imprinted in Prader–Willi Syndrome Induces Aberrant Apical–Basal Polarization and Oxidative Damage in RPE Cells

“…Rapamycin, a drug that works by inhibiting the mTOR pathway, shows protective roles in multiple retinopathies, including AMD. 39 , 40 We herein further annotated whether IPW mediates RPE features through the AKT/mTOR pathway using rapamycin. Our data implied that rapamycin suppresses the IPW mediated activation of the AKT/mTOR pathway in fRPE cells ( Fig.…”

Nutritional Factors: Benefits in Glaucoma and Ophthalmologic Pathologies

“…Anti-proliferative properties of RAPA have been observed to prevent the proliferation of human retinoblastoma cells [ 125 ]. General strategies targeting the mTOR signaling pathway have been determined to possess viable therapeutic potentials for managing ocular neurodegenerative disorders [ 126 ]. The in vivo application of RAPA was correlated with the partial reversal of metabolic failure via the loss of complement factor H in retinal pigment epithelial cells, which is an important pathophysiological contributor to photoreceptor degeneration in ARMD [ 127 ].…”

Einflussnahme des Diabetes mellitus auf glaukomrelevante Untersuchungsergebnisse beim primären Offenwinkelglaukom

“…Unterstützend kommt hinzu, dass durch den oxidativen Stress ein Protein namens mTOR (Mechanistic Target of Rapamycin) aktiviert wird, eine Serin-Threonin-Kinase, die in unterschiedliche Signalwege von Wachstumsfaktoren, Energiehaushalt und Sauerstoffkonzentration in der Zelle eingebunden ist. Durch seine Überaktivierung kann es zu einer verstärkten Apoptose kommen, welche die Neurodegeneration in der Netzhaut und im Sehnerv begünstigt 35 , 36 .…”

“…In addition, the oxidative stress activates a protein called mTOR (mechanical target of rapamycin), a serine/threonine kinase that is involved in different signaling pathways of growth factors, energy balance, and oxygen concentration in the cell. Its overactivation can lead to increased apoptosis, which favors neurodegeneration in the retina and optic nerve 35 , 36 .…”