Aldehyde Dehydrogenase and Aldo-Keto Reductase Enzymes: Basic Concepts and Emerging Roles in Diabetic Retinopathy

Antioxidants (Basel). 2023 Jul 21;12(7):1466. doi: 10.3390/antiox12071466.

Abstract

Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression of the disease. The elimination and processing of aldehydes in the retina rely on the crucial role played by aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. This review article investigates the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the advancement of DR. It also provides an overview of the ALDH and AKR enzymes expressed in the retina, emphasizing their growing importance in DR. Understanding the relationship between aldehyde metabolism and DR could guide innovative therapeutic strategies to protect the retina and preserve vision in diabetic patients. This review, therefore, also explores various approaches, such as gene therapy and pharmacological compounds that have the potential to augment the expression and activity of ALDH and AKR enzymes, underscoring their potential as effective treatment options for DR.

Keywords: aldehyde dehydrogenase; aldo-keto reductase; diabetic retinopathy; lipid peroxidation; oxidative stress.

Publication types

  • Review

Grants and funding

B.M.K. was supported by funding from The Republic of Turkey Ministry of National Education. K.L. was supported by the RECOGNISED consortium grant (EU GA 847749). J.A. was supported by a research grant from Diabetes UK (18/0005791).