# The Relationship between Mitochondria and Neurodegation in the Eye: A Review
### Other Cells of the Inner Retina  
The superoxide dismutase (SOD) family is an important antioxidant system, and a deficiency of Cu- and Zn-superoxide dismutase (SOD1) in mice can lead to a variety of phenotypes that are similar to accelerated aging. Some studies have found that, after SOD1 aging, the cells of the inner and outer nuclear cell layers swell and the intracellular mitochondria are degraded. When the activity of manganese superoxide dismutase (MnSOD) and its mRNA expression were decreased, mitochondrial function was impaired, and the inner nuclear layer (INL) was thinned [8; 9; 10; 11]. Reductions in mitochondrial volume and distribution may indicate that retinal ganglion cells in glaucoma are in a state of increased metabolic strain. Genomic analysis revealed that many instances of retinal endometrial cell apoptosis were caused by mutations in mitochondrial genes or nuclear genes encoding mitochondrial proteins [12]. A loss-of-function mutation in the retinal degenerative change 3 (RD3) gene resulted in hereditary retinopathy with impaired rod and cone function. Guanylate-cyclase-activated proteins (GCAPs) may be the key Ca\({}^{2+}\) sensors mediating the physiopathology of this disease. GCAPs induce endoplasmic reticulum (ER) stress, mitochondrial swelling, and cell death. Endoplasmic reticulum stress and mitochondrial swelling are early markers before the death of RD3 retinal photoreceptors [13; 14]. OPA1 is a major gene that leads to optic nerve atrophy (DOA). OPA1 encodes dynamin in mitochondria, supports the intimal structure, and is widely expressed [8; 9]. The glutamate receptor initiates acute intraocular hypertension, and ischemic injury induces the retinal mitochondria to release OPA1 and activate the cell death pathway, resulting in the apoptosis of inner retinal cells [15; 16; 17]. A decrease in oxygen consumption (QO2) at the synaptic terminal of the retina and photoreceptors indicates the continued dysfunction of mitochondrial oxidative phosphorylation, the activation of apoptotic pathways, and the apoptosis of retinal endometrium cells [18]. Retinal edema, vacuolation, and the mitochondrial disintegration of retinal cells were observed upon the intravitreal injection of methotrexate in rabbits. After continuous injection, the edema of the photoreceptors and the nucleus and ganglion cell layers were affected, leading to nuclear degeneration in the outer nuclear layer and damage to the photoreceptor layer [19]. Many studies have shown that the overactivation of NMDA receptors leads to a calcium overload in retinal ganglion neurons and defects in the mitochondrial respiratory chain, which promote neurodegenerative diseases, such as glaucoma. Calcium can induce transient hyperpolarization of the mitochondrial membrane potential, trigger the release of reactive oxygen free radicals, and lead to the apoptosis of inner retinal cells [20; 21; 22]. REEP6 plays an important role in maintaining cGMP homeostasis by promoting the stabilization and/or transportation of guanylate cyclase and maintaining homeostasis in the endoplasmic reticulum and mitochondria; it also plays a protective role in retinal endomyocytes [23]. Nuclear respiratory factor 1 (NRF1) was found to be significantly inhibited by the proliferation of retinal progenitor cells (RPCs) and post-mitotic rod photoreceptor cells (PRSs) in vivo. These results suggest that the NRF1-mediated disruption of mitochondrial biogenesis leads to mitochondrial damage and the slow, progressive degeneration of PRSs in rod cells [24]. The OTX2 (orthodentile homeobox 2) haploid defect leads to various developmental defects in the mammalian visual system, such as retinal dysfunction and the absence of eyes. The OTX2 protein is localized to the mitochondria of bipolar cells and promotes ATP synthesis. As part of the mitochondrial ATP synthase complex, retinal dystrophy in OTX2 +/GFP heterozygous knockout mice was mainly due to bipolar cell loss due to mitochondrial damage [25; 26; 27].