Substances of Interest That Support Glaucoma Therapy

Abstract

Glaucoma is a multifactorial disease in which pro-apoptotic signals are directed to retinal ganglion cells. During this disease the conventional outflow pathway becomes malfunctioning. Aqueous humour builds up in the anterior chamber, leading to increased intraocular pressure. Both of these events are related to functional impairment. The knowledge of molecular mechanisms allows us to better understand the usefulness of substances that can support anti-glaucoma therapy. The goal of glaucoma therapy is not simply to lower intraocular pressure; it should also be to facilitate the survival of retinal ganglion cells, as these constitute the real target tissue in this disease, in which the visual pathway is progressively compromised. Indeed, an endothelial dysfunction syndrome affecting the endothelial cells of the trabecular meshwork occurs in both normal-tension glaucoma and high-tension glaucoma. Some substances, such as polyunsaturated fatty acids, can counteract the damage due to the molecular mechanisms - whether ischemic, oxidative, inflammatory or other - that underlie the pathogenesis of glaucoma. In this review, we consider some molecules, such as polyphenols, that can contribute, not only theoretically, to neuroprotection but which are also able to counteract the metabolic pathways that lead to glaucomatous damage. Ginkgo biloba extract, for instance, improves the blood supply to peripheral districts, including the optic nerve and retina and exerts a neuro-protective action by inhibiting apoptosis. Polyunsaturated fatty acids can protect the endothelium and polyphenols exert an anti-inflammatory action through the down-regulation of cytokines such as TNF-α and IL-6. All these substances can aid anti-glaucoma therapy by providing metabolic support for the cells involved in glaucomatous injury. Indeed, it is known that the food we eat is able to change our gene expression.

Relationships between Obesity, Nutrient Supply and Primary Open Angle Glaucoma in Koreans

“…Unlike POAG with high IOP, an IOP-independent mechanism contributes to pathogenesis of this disease [28]. Many factors such as genetics, age, and exogenous and endogenous factors affect the development and progression of POAG [29]. Oxidative stress is known to induce molecular damage in neuronal endothelial cells and to trigger events that lead to glaucoma [29].…”

“…Many factors such as genetics, age, and exogenous and endogenous factors affect the development and progression of POAG [29]. Oxidative stress is known to induce molecular damage in neuronal endothelial cells and to trigger events that lead to glaucoma [29]. Moreover, because neurons in the brain do not regenerate, the accumulation of damage may exceed the capacity of repair mechanisms, leading to glaucoma [30].…”

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury

“…Among Gangliomix components, Neumentix is a spearmint extract rich in polyphenols and rosmarinic acid that has been demonstrated to improve working memory and attention by reducing oxidative stress thus possibly counteracting neuron degeneration [33]. No information is available on Neumentix efficacy in degenerative pathologies of the retina, although there are indications that polyphenols, acting as anti-inflammatory and antioxidant compounds, can aid anti-glaucoma therapy by providing metabolic support to the cells involved in glaucomatous injury [54]. Among polyphenols, flavonoids demonstrate protective effects on RGC death by reducing inflammation and oxidative stress in cell culture as well as in the ONC model [22].…”

Novel therapies for glaucoma: a patent review (2013-2019)

“…From a medicinal chemistry point of view, the inventors not only aimed at improving the efficacy, but also the metabolic stability of their chemical scaffolds (usually based on the carbamate function). All these targets have been studied for their efficacy alone or in combination with other agents (e.g., FAAH and MAGL inhibitors[78]) to better achieve the therapeutic goal.Conversely, in our opinion, little interest has been focused on the future of glaucoma therapy related to the specificity of each individual patient (e.g., genetic make-up), Toll-like receptors (TLRs) crucial for the production of inflammatory cytokines and up-regulated by elevated IOP in human glaucomatous eye[79], neuroinflammation[80], and the beneficial neuroprotective impact on the outflow channel and to the optic nerve of the dietary antioxidant components such as polyunsaturated fatty acids, Ginkgo biloba leaf or bilberry extract, and other plant polyphenols[81]. Recently, the promising results of a multicenter, controlled trial corroborated the neuroprotective effects of Coqun ® , an ophthalmic solution of Coenzyme q10 and Vitamin E, in patients affected by primary open-angle glaucoma, registered in previous pre-clinical studies and small non-controlled clinical trials both in vitro and in vivo[82].…”