Contribution of TNF-α to the development of retinal neurodegenerative disorders

During the late 1970s, tumor necrosis factor alpha (TNF-alpha) was initially recognized as an endotoxin-induced substance that was mainly produced by macrophages, and able to cause the lysis of certain tumor cells. Subsequent research demonstrated that TNF-alpha mediates a broad range of cellular activities, including proliferation, survival, differentiation and apoptosis. It is also considered to be essential for the induction and maintenance of the inflammatory immune responses. Meanwhile, visual impairment imposes a substantial disease burden on society. It is associated with both significant economic impact and reduction in quality of life. Visual impairment raises serious social challenges for both patients and their families, interfering with day-to-day life, and can limit employment possibilities. Many of the most common, irreversible blinding pathologies involve neuronal loss from the retina, which is the light-sensing tissue of the eye. The retina, being part of the central nervous system, is unable to regenerate neurons lost to disease. Therefore, in the current review we will discuss the association between increased expression of TNF-alpha with neurodegenerative disorders, downstream cellular signaling mechanisms following interaction of TNF-alpha with its receptors, and the role of TNF-alpha as a possible target in the treatment of retinal neurodegenerative disorders.