The Role of Glutathione in Age-Related Macular Degeneration (AMD)

Int J Mol Sci. 2024 Apr 9;25(8):4158. doi: 10.3390/ijms25084158.

Abstract

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet-progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye.

Keywords: AMD; GSTM1; GSTT1; age-related macular degeneration; glutathione (GSH); glutathione S-transferase (GST); glutathione peroxidase (GPx); glutathione reductase (GR); oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Glutathione Transferase* / genetics
  • Glutathione Transferase* / metabolism
  • Glutathione* / metabolism
  • Humans
  • Macular Degeneration* / genetics
  • Macular Degeneration* / metabolism
  • Macular Degeneration* / pathology
  • Oxidative Stress

Substances

  • Glutathione
  • Glutathione Transferase

Grants and funding

This research received no funding. The authors declare no competing financial interests. The authors declare that this research did not receive any specific funding.