The Role of Autophagy in Glaucomatous Optic Neuropathy

Abstract

Autophagy is a conserved lysosomal-dependent pathway responsible for the degradation of cytoplasmic macromolecules. Based on the mechanism of cargo delivery to lysosomes, mammalian cells can undergo micro, macro, and chaperonemediated autophagy. Other than physiological turnover of proteins and organelles, autophagy regulates cellular adaptation to different metabolic states and stressful conditions by allowing cellular survival or, when overactivated, participating to cell death. Due to their structure and function, neurons are highly dependent on autophagy efficiency and dysfunction of the pathway has been associated with neurodegenerative disorders. Glaucomatous optic neuropathies, a leading cause of blindness, are characterized by the progressive loss of a selective population of retinal neurons, i.e., the retinal ganglion cells (RGCs). Here we review the current literature on the role of autophagy in the pathogenic process that leads to the degeneration of RGC in various experimental models of glaucoma exploring the modulation of the pathway as a potential therapeutic intervention.

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

“…Overall, an impairment of autophagy due to oxidative stress is related with several age-related eye diseases such as dry eye diseases, corneal dystrophy type 2, cataracts and retinal dystrophies like AMD, glaucoma, DR, and retinal artery occlusion [51,52].…”

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

“…Potentially, the balance between autophagy and microglia can be regulated by pharmacological inhibition of, e.g., 3-methyladenine. Finally, studies indicate that some humans are genetically impaired of basal autophagy, which can impact retinal homeostasis and potentially promote retinal neurodegeneration, hereunder glaucoma ( 162 – 164 ). Future studies are needed to investigate further the partnership between autophagy and microglia as well as to elucidate further the interaction between microglia as well as other glia subtypes and RGCs.…”

Intravitreous delivery of melatonin affects the retinal neuron survival and visual signal transmission: in vivo and ex vivo study

“…RGCs project their 1.2 million axons, composing the optic nerve, to the brain, transmitting the visual signals gathered by the retina, ultimately leading to formed vision in the visual cortex (Maresca et al., 2013 ; Carelli et al., 2017 ). Loss of RGCs is a common feature of optic neuropathies (Adornetto et al., 2020 ). It has been reported that the combined use of melatonin and Zoloft can result in the melatonin/dopamine imbalance in retina, manifesting as a toxic optic neuropathy (Lehman & Johnson, 1999 ).…”