Neuroprotection in glaucoma: old concepts, new ideas

Abstract

Introduction: The disease process of glaucoma is thought to begin up to twenty years before a diagnosis can be made. While its current treatment paradigm seeks to reduce the rate of disease progression through reducing intraocular pressure, these interventions are of limited effectiveness and are typically made late. Together, this highlights an unmet clinical need for development of novel techniques to facilitate the early diagnosis of glaucoma and the emergence of new treatment paradigms. This review provides a summary of recent developments in the early diagnosis and treatment of glaucoma, including updates on natural neuroprotective compounds. Areas covered: A systematic review of the glaucoma literature was conducted including the keywords retinal ganglion cell apoptosis, neuroprotection, resveratrol, curcumin, adaptive optics, and detection of apoptosing retinal cells (DARC). Expert commentary: While a growing number of pre-clinical studies have reported efficacy of neuroprotective interventions for the treatment of glaucoma, these technologies have not yet translated into clinical use. A likely explanation for this phenomenon is the relatively late stage at which glaucoma is currently diagnosed in patients. The development of techniques to diagnose glaucoma earlier in the disease process would enable the earlier administration of neuroprotective interventions which could slow glaucoma-associated vision loss.

Curcumin as a Therapeutic Option in Retinal Diseases

“…The authors also noticed that the use of high concentrations of curcumin inhibited not only apoptosis but also necrosis on TMCs [59]; which somehow contradicts another findings reviewed herein, such as the one stated by Park [52]. Furthermore, curcumin has proved to increase viability of RGC in other ocular diseases as described on the RIRI section of this review [53]. Curcumin has also been used to treat glaucoma in form of loaded nanoparticles [60], but this will be discussed later.…”

“…Glaucoma is one of the major causes of irreversible blindness, with over 60 million people affected worldwide and steadily growing [53,54]. It is a progressive optic neuropathy, characterized by the excavation of the optic nerve, due mainly to high ocular pressure, which leads to a progressive visual field loss by the loss of RGCs [55].…”

Treating the whole glaucoma spectrum: A new treatment approach is required

“…To target these pathways, studies using models of glaucoma have shown promising results trialling neuroprotective therapies. Such agents include memantine that inhibits glutamate signalling, coenzyme Q10 as an anti‐oxidant and brimonidine which aside from its anti‐ocular hypertensive properties has long been proposed to possess neuroprotective effects 3 . Although clinical trials have shown promising initial results with coenzyme Q10 and brimonidine, large randomized controlled trials have failed to show efficacy 4 .…”

“…To complicate matters, trial‐related factors have been discussed as alternative explanations for these findings 5 . Recently, there has been renewed interest in compounds historically valued as medicinal, including curcumin found in turmeric and resveratrol contained in dark chocolate and red wine 3 . Both these compounds are thought to provide anti‐oxidant and anti‐inflammatory properties; however, their poor bioavailability has limited their use.…”

Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration

“…For these patients, nothing can be done to preserve vision because effective neuroprotective treatments do not exist. Furthermore, advances in the field are allowing for earlier diagnosis of glaucoma, at stages where neuroprotective intervention could have a greater impact on visual outcomes [4]. For these reasons, recent glaucoma research has focused on defining mechanisms of pathogenesis as well as developing and testing cell-based treatments that protect visual neurons.…”