Tackling retinal ganglion cell apoptosis in glaucoma: role of adenosine receptors

Expert Opin Ther Targets. 2021 Jul;25(7):585-596. doi: 10.1080/14728222.2021.1969362. Epub 2021 Aug 24.

Abstract

Introduction: The role of adenosine receptors as therapeutic targets for neuroprotection is now widely recognized. Their role, however, in protection against retinal ganglion cell (RGC) apoptosis in glaucoma needs further investigation. Hence, in this review, we look into the possibility of adenosine receptors as potential therapeutic targets by exploring their role in modulating various pathophysiological mechanisms underlying glaucomatous RGC loss.

Areas covered: This review presents a summary of the adenosine receptor distribution in retina and the cellular functions mediated by them. The major pathophysiological mechanisms such as excitotoxicity, vascular dysregulation, loss of neurotrophic signaling, and inflammatory responses involved in glaucomatous RGC loss are discussed. The literature showing the role of adenosine receptors in modulating these pathophysiological mechanisms is discussed. The literature search was conducted using Pubmed search engine using key words such as 'RGC apoptosis,' 'adenosine,' adenosine receptors' 'retina' 'excitotoxicity,' 'neurotrophins,' 'ischemia', and 'cytokines' individually and in various combinations.

Expert opinion: Use of adenosine receptor agonists and antagonists, for preservation of the RGCs in glaucomatous eyes independent of the level of intraocular pressure seems a very useful strategy. Future application of this strategy would require appropriate designing of drug formulation for tissue and disease-specific receptor targeting. Furthermore, the modulation of physiological functions and potential adverse effects need further investigations.

Keywords: Adenosine receptors; excitotoxicity; glaucoma; neuroprotection; neurotrophin; retina; retinal ganglion cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Glaucoma* / drug therapy
  • Humans
  • Intraocular Pressure
  • Receptors, Purinergic P1 / therapeutic use
  • Retinal Ganglion Cells* / physiology

Substances

  • Receptors, Purinergic P1