# The Relationship between Mitochondria and Neurodegation in the Eye: A Review
## 3 Impaired Mitochondrial Function in Aging and Glaucoma
### How Aging Affects Mitochondrial Function  
Genomic instability in mitochondria is one of the contributing factors for age-related retinal pathophysiology [34]. Mitochondria have their own circular mtDNA, which is \(\sim\)16.5 kb. The mtDNA lacks protective proteins, such as histone and non-histone proteins, and its structure makes it extremely vulnerable to oxidative damage [35]. ROS damage and mtDNA mutations form a vicious cycle and promote each other. It is a significant phenomenon that retrograde communication can increase oxidative mtDNA damage [36]. With an increase in age, the mitochondrial DNA oxidation level increases, which affects the transcription and replication of mitochondrial DNA and further changes the functions of mitochondrial proteins [37]. Mitochondrial stress response pathways can regulate the aging process [38]. As they provide energy to cells, mitochondria lead to increased levels of reactive oxygen species and oxidative stress products; this process is one of the main drivers of aging [39]. Declines in mitochondrial quality and activity affect not only normal aging, but also a range of age-related diseases [40]. Mitochondrial dysfunction and altered mitochondrial dynamics are some of the main causes of aging and age-related diseases [41]. Mitochondrial autophagy is a special form of autophagy that regulates mitochondrial dysfunction and damage. Reduced mitochondrial autophagy and phagocytosis play an important role in neurodegenerative diseases [42] (Figure 1). Figure 1: Relationship between aging and mitochondrial dysfunction. Aging can increase the oxidative damage of MtDNA and MtDNA alternations, leading to mitochondrial dysfunction that increased ROS and reduced ATP. Finally, aging and MtDNA alternations affected each other. A large number of Ca\({}^{2+}\) flowed into mitochondrial, causing mitochondrial Ca\({}^{2+}\) overload, leading to dysfunction of the electron transport chain, which increased ROS and reduced ATP that promoted aging. The inner mitochondrial membrane is the main source of superoxide, which can produce a large amount of hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), which can further react to form a hydroxyl radical (HO\(\bullet\)). The outer mitochondrial membrane can catalyze the oxidation and deamination of biogenic amines and is the source of a large quantity of H\({}_{2}\)O\({}_{2}\). These toxic reactions significantly contribute to the aging process and form the central tenet of the \"free radical theory of aging\". The mtDNA is a key cellular target for ROS, and the chronic ROS exposure found in several aging-related degenerative diseases leads to decreased mitochondrial function, increased mitochondrial production of ROS, and persistent mitochondrial DNA damage. Poly has been identified as one of the major oxidative mitochondrial matrix proteins. As a target for oxidative damage, Poly can partially damage mitochondrial function by increasing oxidative stress, ultimately leading to a reduction in mitochondrial DNA replication and repair ability [43; 44]. Previous studies have found that ROS production in cells can be regulated by regulating mitochondrial activity. Adenosine A2A receptor (A2 AR) stimulation enhances mitochondrial metabolism and reduces the mitochondrial damage mediated by reactive oxygen species [45; 46]. The mitochondrial electron transport chain is a highly efficient multifunctional system that can oxidize one glucose molecule to produce 38 ATP molecules. Mitochondrial electron transport chains can produce side reactions, such as those for superoxide anion radicals (O\({}^{2}\bullet\)) and hydroxyl radicals (HO\(\bullet\)), resulting in reduced production of ATP and oxidative overload. Studies have confirmed that, in mitochondrial DNA, mitochondrial autophagy, mutations, biological failure which can be defined as the inadequacy of the host tissue to establish or to maintain, abnormal metal homeostasis, and other factors lead to electron leakage in the mitochondrial electron transport chain [47].