Innovations and revolutions in reducing retinal ganglion cell loss in glaucoma

ABSTRACT

Introduction

Glaucoma remains the leading cause of irreversible blindness. Although the loss of retinal ganglion cells (RGCs) is an established hallmark of glaucoma, reduction of intraocular pressure (IOP) is a widely used evidence-based management approach, even in normotensive patients. However, despite optimal pressure control, some patients progress to lose vision.

Areas covered

This review provides a summary of the latest methods aimed at reducing RGC loss with the objective of preserving vision, categorized by the mechanism of action. We discuss both the newest ways in which IOP can be reduced, alongside ‘pressure-independent’ pharmacological therapies and developments in bioengineering. The conducted PubMed search included the terms: ‘glaucoma pathophysiology,’ ‘IOP-lowering agents,’ ‘retinal ganglion cell apoptosis,’ ‘neuroprotection,’ ‘stem cells,’ ‘imaging.’

Expert opinion

With many agents failing to successfully translate into clinical use, further understanding of the underlying disease process is required, along with novel biomarkers that will enable timely and reliable quantification of treatment effect.

KEYWORDS:

• Apoptosis
• excitotoxicity
• glaucoma
• neuroprotection
• neurotrophic factors
• stem cells

Article highlights

• The pathophysiology of glaucoma comprises a network of interacting pathways that must be carefully considered when identifying novel therapeutic targets and developing treatments.

• Excitotoxic RGC stimulation could potentially increase nuclear translocation of histone deacetylases, repressing the transcription of certain genes, as seen in the early stages of RGC apoptosis. Further study of this pathway is required for the identification of efficacious therapeutic targets.

• Retinal bioenergetic research is gaining increasing interest in glaucoma, with monocarboxylate transporter-2 and insulin signaling having recently been identified as potential therapeutic targets.

• Cell and genetic therapies could provide a stable source of neurotrophic factors, with clinical trials currently underway.

• The mechanisms of action of some traditional IOP-lowering therapies (such as alpha-2 agonists, prostaglandin analogs, and carbonic anhydrase inhibitors) are being re-assessed to evaluate their potential as dual-action agents with both IOP-lowering and neuroprotective properties.

• Advances in knowledge of metabolomics, genetics, and imaging could provide future biomarkers for research and enable accurate risk stratification of patients, allowing for more personalized and targeted therapy.

Declaration of interest

MF Cordeiro is a named co-inventor on a granted patent EP 2231199B1 and published patent WO 2011055121A1 owned by UCL and related to DARC technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript is not funded.