Mechanisms of age-related ocular diseases: a comprehensive review with an emphasis on glaucoma

With aging, senescence(definition)-related diseases are increasing in prevalence. The senescence of cells in the central nervous system has been linked with the development of neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. These changes are not limited to the brain as many eye diseases, such as cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma, are also age-related. Among them, glaucoma is one of the leading causes of irreversible blindness with a multifactorial neurodegenerative nature. Besides an elevated intraocular pressure, an increased age is one of the main risk factors for this disease. Hence, in this review, we will discuss age-related changes in the context of eye disease, with a specific focus on glaucoma. Several general aging mechanisms were put forward in different eye diseases. This includes dysregulated nutrient sensing, cellular senescence, stem cell exhaustion, altered intercellular communication, genomic instability, telomere(definition) shortening, epigenetic alteration, loss of proteostasis(definition), compromised autophagy(definition), and mitochondrial dysfunction(definition). In glaucoma, aging is a main risk factor for the development. This is triggered by oxidative, metabolic, immunological, and biomechanical stressors with many cross-talks. Oxidative stress, for example, can also trigger apoptotic cell death through mitochondrial damage, hypoxia, inflammation, and endothelial dysregulation. Also, with advanced age, alterations in extracellular matrix composition and structure are becoming important biomechanical contributing factors to the pathology of glaucoma. All mentioned mechanisms triggered by aging processes are generally accepted as contributing factors in the development of glaucoma in the aged eye. A better understanding of these will help to find novel therapeutic approaches for glaucoma patients in the future.