# The Relationship between Mitochondria and Neurodegation in the Eye: A Review
## 3 Impaired Mitochondrial Function in Aging and Glaucoma
### How Elevated Intracular Pressure (IOP) Affects Mitochondrial Function  
Mitochondrial autophagy is a type of mitochondrion-specific autophagy, which is an important part of mitochondrial quality control and a collective mechanism that is responsible for the homeostasis of this organelle [69]. The activation of autophagy occurs before the process of apoptosis and is partly mediated by reactive oxygen species and the formation of mitochondrial permeability transition pores. The formation of mitochondrial permeability transition pores is directly related to the autophagy induced by 3 NP treatment [70]. Phosphorylated ubiquitin may act as a receptor. After effectively stabilizing and activating OMM, Parkin ubiquitinates a large number of OMM proteins, which, in turn, attract specific autophagy receptors, thus triggering autophagy. AMP activates protein kinase (AMPK), insulin-like signaling (ILS) pathways, and the signaling cascades triggered by calcium and nitric oxide, which, in turn, lead to mitochondrial protein folding; these proteins are directed to different mitochondrial sub-compartments depending on the folded sequence: the outer mitochondrial membrane (OMM), intermembrane space (IMS), inner mitochondrial membrane (IMM), or matrix [71]. TFEB is activated after mitochondrial autophagy in order to maintain the ALP and mitochondrial biogenesis. The level of PGC-1\(\alpha\) (peroxisome proliferatorator-activated receptorycoactivator-1, PGC-1) mRNA in cells with increased TFEB protein is significantly increased. PGC-1\(\alpha\) mRNA is a regulator of mitochondrial biogenesis and leads to increased mitochondrial content [72]. Elevated intraocular pressure (IOP) can affect mitochondrial division, induce the release of optic atrophy type 1 (OPA1), and directly damage the optic nerve head (ONH) axons [73; 74; 75]. Inhibitory glutamate receptor activation inhibits the release of OPA1 in mitochondria induced by acute IOP elevation; thus, glutamate receptors' activation of acute IOP elevation may lead to mitochondrion-mediated cell death pathways in the ischemic retina [17; 76] (Figure 2). Increased mitochondrial OPA1 may provide an important cellular defense mechanism against stress-mediated retinal damage [77]. Some studies have shown that the early modulation of gene expression changes the retinal ganglion cell layer (GCL) in mouse models of glaucoma. Genes downregulated in the mitochondria are involved in the metabolic pathway and influence retinal ganglion cells [78]. Neuroglobin (NGB) is a newly discovered member of the globulin superfamily. As an endogenous neuroprotectant, it can reduce oxidative stress and improve mitochondrial function, thus promoting the survival of RGCs [79; 80]. It was found that p62 was present in the mitochondria of retinal ganglion cells (RGC-5), and large amounts of nicotinamide mononucleotide adenylyl transferase 3 (Nmnat3) and p62 were co-localized in the mitochondria. Nmnat3 transfection can reduce the p62 of RGC-5 cells and increase autophagic flux. The regulation of Nmnat3 and autophagy may induce optic neurodegenerative diseases [81]. Elevated acute IOP significantly increases the expression of the retinal mitochondrial transcription factor A (TFAM) protein, which regulates the copy number and transcriptional activity of mitochondrial DNA, participates in cell apoptosis, and affects the axonal regeneration of the optic nerve [82]. Dynamic changes in mitochondria (MT) induced by elevated intraocular pressure are involved in the occurrence and development of neurodegenerative diseases. In a glaucoma mouse model (DBA/2J (D2)), DRP1 (dynamin-related protein 1) inhibition promoted RGC survival by increasing the phosphorylation of BAD (B lymphoma-2 gene related promoter) at serine 112 in the retina. The RGCs' axons are preserved by the maintenance of the integrity of the MT of the glial layer [83; 84; 85]. Progressive swelling of the mitochondria following elevated intraocular pressure causes severe structural changes, leading to the death of RGCs [86; 87; 88].