Dysregulation of histone deacetylases in ocular diseases

Arch Pharm Res. 2024 Jan;47(1):20-39. doi: 10.1007/s12272-023-01482-x. Epub 2023 Dec 27.

Abstract

Ocular diseases are a growing global concern and have a significant impact on the quality of life. Cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy are the most prevalent ocular diseases. Their prevalence and the global market size are also increasing. However, the available pharmacotherapy is currently limited. These diseases share common pathophysiological features, including neovascularization, inflammation, and/or neurodegeneration. Histone deacetylases (HDACs) are a class of enzymes that catalyze the removal of acetyl groups from lysine residues of histone and nonhistone proteins. HDACs are crucial for regulating various cellular processes, such as gene expression, protein stability, localization, and function. They have also been studied in various research fields, including cancer, inflammatory diseases, neurological disorders, and vascular diseases. Our study aimed to investigate the relationship between HDACs and ocular diseases, to identify a new strategy for pharmacotherapy. This review article explores the role of HDACs in ocular diseases, specifically focusing on diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity, as well as optic nerve disorders, such as glaucoma and optic neuropathy. Additionally, we explore the interplay between HDACs and key regulators of fibrosis and angiogenesis, such as TGF-β and VEGF, highlighting the potential of targeting HDAC as novel therapeutic strategies for ocular diseases.

Keywords: Aged-macular degeneration; Diabetic retinopathy; Glaucoma; Histone deacetylase; Ocular disease; Optic neuropathy; Retinitis pigmentosa; Retinoblastoma; Retinopathy of prematurity; TGF-β; VEGF.

Publication types

  • Review

MeSH terms

  • Diabetic Retinopathy* / drug therapy
  • Glaucoma* / drug therapy
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Deacetylases / metabolism
  • Humans
  • Infant, Newborn
  • Macular Degeneration*
  • Quality of Life

Substances

  • Histone Deacetylases
  • Histone Deacetylase Inhibitors