Managing Intraocular Pressure: Innovation in Glaucoma Management

Abstract

Primary open-angle glaucoma is a progressive ocular neuropathy that if left untreated may lead to blindness. The main risk factor for developing glaucoma is increased intraocular pressure. Intraocular pressure is regulated by the balance of aqueous humour synthesis and secretion into the eye and outflow from the eye; therefore, most therapies for glaucoma seek lowering intraocular pressure to avoid disease progression. There are several types of drugs in the market for the treatment of glaucoma, but there are still unmet needs to be overcome; therefore, significant effort has been put in the last few years to develop new medicines with innovative mechanisms of action as well as devices to improve quality of life in glaucoma patients. The present review offers a thorough revision of the latest advances in the glaucoma therapy field, focusing on innovative approaches, new targets and new mechanisms of action.

Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment

“…Flavonoids in Gingko biloba L. may attenuate RGC injuries in glaucoma by suppressing ROS-induced apoptosis [236]. However, a clinical study comparing oral antioxidants, including extracts of Ginkgo biloba and α-tocopherol, for the treatment of glaucoma (NCT01544192) did not show any clear benefits associated with the use of Ginkgo biloba [237]. Coenzyme Q 10 , another flavonoid, has been shown to reduce glutamate excitotoxicity and ROS formation in a mice model of glaucoma, thus preserving RGCs from apoptosis by reducing Bax expression and enhancing Bad protein expression [238].…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…PERK activates eukaryotic initiation factor 2α (eIF2α), which downregulates overall protein translation, indirectly protecting the cell from protein misfolding [235]. PERK also upregulates activating transcription factor 4 (ATF-4), which triggers the CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), exerting a proapoptotic function [240]. In this regard, Han et al demonstrated that a sustained activation of ATF-4 and CHOP increases protein synthesis and leads to cell death through oxidative stress and ATP depletion [236].…”

“…These interactions suggest that Gingko biloba extracts may reduce RGC damage in glaucoma by inhibiting H 2 O 2 -related apoptosis through pathways involving p53, Bax/Bcl-2, and caspase-3/9 [265]. A dedicated clinical trial evaluated the use of oral antioxidants for glaucoma, comparing extracts of Gingko biloba with α-tocopherol for 3 months (NCT01544192), and completed phase III, reporting no clear clinical benefit for the use of Gingko biloba [240]. Another flavonoid, coenzyme Q 10 , a natural lipophilic compound, has demonstrated in murine glaucoma models its ability to reduce glutamate excitotoxicity and oxidative stress, promoting RGC survival and preventing apoptotic cell death by decreasing Bax expression and increasing the Bcl-2 associated agonist of cell death (Bad) protein expression [266].…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…These interactions suggest that Gingko biloba extracts may reduce RGC damage in glaucoma by inhibiting H₂O₂-related apoptosis through pathways involving p53, Bax/Bcl-2, and caspase-3/9 [272]. A dedicated clinical trial evaluated the use of oral antioxidants for glaucoma, comparing extracts of Gingko biloba with α-tocopherol for 3 months (NCT01544192), and completed phase III, reporting no clear clinical benefit for the use of Gingko biloba [273]. Another flavonoid, coenzyme Q₁₀, a natural lipophilic compound, has demonstrated in murine glaucoma models its ability to reduce glutamate excitotoxicity and oxidative stress, promoting RGC survival and preventing apoptotic cell death by decreasing Bax expression and increasing the Bcl-2 associated agonist of cell death (Bad) protein expression [274].…”