Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia‐induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti‐inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia‐induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia‐induced injuries of the central nervous system (CNS).

Glaucoma is a globally unmet medical challenge and the most prevalent neurodegenerative disease, which permanently damages the optic nerve and retinal ganglion cells (RGCs), leading to irreversible blindness. Present therapies target solely at lowering intraocular ocular pressure (IOP), a major risk factor of the disease; however, elevated IOP is neither necessary nor sufficient to cause glaucoma. Glaucomatous RGC and nerve fiber loss also occur in individuals with normal IOP. Recent studies have provided evidence indicating a link between elevated IOP and T cell-mediated autoimmune responses, particularly that are specific to heat shock proteins (HSPs), underlying the pathogenesis of neurodegeneration in glaucoma. Reactive glial responses and low-grade inflammation may initially represent an adaptive reaction of the retina to primary stress stimuli; whereas, sustained and excessive glial reactions lead to expanded immune responses, including adaptive immunity, that contribute to progressive neural damage in glaucoma. Emerging data suggest a similar mechanism in play in causing neurodegeneration of other forms of optic neuropathy, such as that resulted from acute ischemia and traumatic injuries. These studies may lead to the paradigm shift and offer a new basis for the development of novel mechanism-based diagnosis, therapy, and preventive interventions for glaucoma. As HSPs are induced under various conditions of neural stress and damage in the brain and spinal cord, these findings may have broader implications for our elucidating of the etiology of other neurodegenerative disorders in the central nervous system.

In developing countries, household air pollution (HAP) resulting from the inefficient burning of coal and biomass (wood, charcoal, animal dung and crop residues) for cooking and heating has been linked to a number of negative health outcomes, mostly notably respiratory diseases and cancers. While ocular irritation has been associated with HAP, there are sparse data on adverse ocular outcomes that may result from acute and chronic exposures. We consider that there is suggestive evidence, and biological plausibility, to hypothesize that HAP is associated with some of the major blinding, and painful, eye conditions seen worldwide. Further research on this environmental risk factor for eye diseases is warranted.