ReviewImmunoregulation of retinal ganglion cell fate in glaucoma
Section snippets
Immunoregulation governs RGC death in glaucoma
It is likely that all experienced glaucoma specialists have treated patients that cause them to question some commonly accepted paradigms of our profession. Consider, for example, the glaucoma patient whose intraocular pressure (IOP) appears to be perfectly controlled at each office visit. Perhaps it is as low as 10 mmHg or is even in single digits, yet continues to manifest progressive nerve loss and visual field deterioration despite having such low pressures. On the other hand, there is the
Retinal ganglion cell fate decisions in glaucoma
An impressive to summarize RGC fate decisions that has been linked to some of the presumptive causative factors of glaucomatous neurodegeneration was depicted by Tatton et al. (2003) as seen in modified form in Fig. 1. As summarized in this figure, cysteine aspartic acid proteases, also known as caspases, are the “executioners” of RGC death, and the key thermostat that regulates caspase activation may be depicted as the relative ratio of two proto-oncogenes known as Bax (which promotes cell
RGC death signaling after axonal injury
Elevated IOP-induced mechanical and/or ischemic injury to RGC axons at the optic nerve head is commonly believed to be the initial injury triggering a sequence of events leading to glaucomatous neurodegeneration at different sub-cellular compartments of RGCs from the retina to the brain. Such an initial injury to RGC axons may result in the blockage of axoplasmic neurotrophin transport to RGC bodies (Anderson and Hendrickson, 1974, Minckler et al., 1976, Quigley and Addicks, 1980, Pease et al.,
Pro-inflammatory cytokines in RGC death
Tumor necrosis factor-alpha (TNF-α) is an inducer of apoptotic cell death through TNF receptor-1 binding. Based on our initial observations that the expression of TNF-α and its death receptor is increased in the glaucomatous retina (Tezel et al., 2001) and optic nerve head (Yan et al., 2000), and that TNF-α exposure results in the apoptotic death of cultured RGCs (Tezel and Wax, 2000a), we have proposed that this pro-inflammatory cytokine may be a mediator of glaucomatous neurodegeneration. In
Is TNF-α involved in neurocytotoxicity of immunesystem cells?
Glial cells, including both macroglial cells (mainly astrocytes) and microglia in the retina and optic nerve head, are the main source of increased TNF-α in glaucomatous eyes (Yan et al., 2000, Tezel et al., 2001). Besides these resident immunoregulatory cells, TNF-α is the most abundantly produced cytokine that is generated by reactive T cells during glia-T cell interactions (Sun et al., 1996, Sun et al., 1997). In addition, another member of the same death receptor family, FasL, have recently
Aberrant immune activity in glaucoma patients
The immune system functions for day-to-day maintenance of the central nervous system functional integrity by providing tissue cleaning and limiting the neurodegenerative consequences of stressful conditions. However, a failure in the regulation of immunity and an immune insufficiency resulting from increased levels of stressful risk factors may turn the protective immunity into an autoimmune neurodegenerative process (Schwartz, 2003, Schwartz and Ziv, 2008). There is now considerable evidence
Heat shock proteins and immune activity
A widespread and chronic tissue stress is evident in the retina and optic nerve head of glaucomatous eyes by a prominent up-regulation of stress proteins, also called HSPs (Tezel et al., 2000). HSPs are among the most highly conserved and abundant proteins in nature and play an important role in cell survival under many environmental stresses as well as under normal conditions. Increased expression of HSPs, particularly including HSP70 and HSP27, is notable in the brain, since both proteins are
Oxidative stress and immune activity
Glial cells exhibit activation in their immunogenic function and antigen presenting ability in glaucoma (Yang et al., 2001b, Tezel et al., 2003). Besides HSPs serving as an early stress response, other constituents of the tissue stress or injury likely act as signals and potential activators of the immune response. For example, reactive oxygen species (ROS) can function as second messengers and modulators of the immune activity (Rutault et al., 1999). ROS and protein oxidation products have
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Age and intraocular pressure in murine experimental glaucoma
2022, Progress in Retinal and Eye ResearchCitation Excerpt :A possible pathway that exacerbates the effects of mitochondrial damage is impairment of antioxidant enzymatic function, such as superoxide dismutase, catalase and glutathione peroxidase due to elevated IOP (Moreno et al., 2004). In glaucoma patients, both innate and adaptative immune responses are reportedly upregulated (Wax and Tezel, 2009). Increased IOP induces production of anti-heat shock protein antibodies, enzymes that counteract the accumulation of dysfunctional proteins (Joachim et al., 2011; Tezel et al., 1998).
Various forms of glaucoma and their treatments
2022, Handbook of Basic and Clinical Ocular Pharmacology and TherapeuticsP2X7 receptor antagonism preserves retinal ganglion cells in glaucomatous mice
2020, Biochemical PharmacologyA neuroglia-based interpretation of glaucomatous neuroretinal rim thinning in the optic nerve head
2020, Progress in Retinal and Eye ResearchNovel inflammatory cytokines (IL-36, 37, 38) in the aqueous humor from patients with chronic primary angle closure glaucoma
2019, International ImmunopharmacologyCitation Excerpt :Similarly there was a significant correlation between IL-38 and MDVF in our current study, which further supports our hypothesis that there is immunological mediated pathogenesis of glaucoma. It has been reported that the release of inflammatory cytokines from damaged RGCs results in MDVF [2,17,24], which is in line with our current finding that there was a correlation between proinflammatory cytokines (IL-36) as well as anti-inflammatory cytokines (IL-37 and IL-38), and MDVF. It is well known that the eye is an immunologically “privilege site”, although it has been demonstrated that there are a number of immunological diseases that involve the eye [25,26].