## 3 Discussion
HSPA9 (Mortalin) is a member of the HSP70 family, which can be inducibly expressed as a direct physiological response to stress [44]. [PERSON] et al. (1995) showed that mortalin is a mitochondrial chaperone protein recently described as a sensor of neuronal stress and involved in protein folding quality control [45, 46]. It is also down-regulated in the neurons of patients with neurodegenerative diseases, such as AD [47] or PD [48, 49]. In an experimental autoimmune encephalomyelitis (EAE) model, mortalin ameliorated mitochondrial dysfunction and visual loss in a gene therapy approach [50, 51, 52]. Studies have shown that mortalin expression levels in neurons directly correlate with mitochondrial stress control, which can also be the occurrence of ROS, as it has already been described for non-neuronal cells and primary cultures of cortical neurons [50, 53]. The increased expression of HSPA9 discussed previously might indicate increased contact sites between mitochondria and ER, resulting in increased Ca\({}^{2+}\) influx into mitochondria [54, 55]. However, an excessive influx of Ca\({}^{2+}\) could lead to apoptosis [56, 57]. Conversely, the adenine nucleoid translocae 2 (ANT2) expression in the DNM1L OS group decreased. This protein is an antiporter by exchanging ADP/ATP within the mitochondrial permeability transition pore complex (MPTP) between the mitochondrial matrix and the cytoplasm [58, 59]. Therefore, ANT2 plays a key role in maintaining mitochondrial membrane potential, regulating the ADP/ATP ratio during oxidative phosphorylation [60, 61]. ANT2 facilitates mitochondrial membrane uncoupling when acetylated by SIRT4, leading to apoptosis [58, 59]. Loss of ANT1 and ANT2 reduces desensitized Ca\({}^{2+}\)-induced MPTP opening in mitochondria [62, 63]. Thus, ANT2 inhibition leads to inhibition of cytochrome c efflux from the inner mitochondrial membrane, which recruits in the suppression of apoptosis [60, 61]. However, at high Ca\({}^{2+}\) concentrations, MPTP could still open [64]. That inhibition of uncoupling proteins in the retina can be protective and has been demonstrated in cell culture experiments [65, 66]. The decreased expression of ANT2 in the DNM1L OS group could reduce apoptosis, which follows the previously discussed increased expression levels of BAD and XIAP. Pathophysiological processes such as oxidative stress or glutamate excitotoxicity lead to increased apoptosis of RGCs in glaucoma [9, 10, 12]. Therefore, it is not surprising that glutamate dehydrogenase (GLUD1) is up-regulated by high IOP and is mainly located in the retinal tissues [67]. In our study, GLUD1 was significantly less abundant in the DNM1L OS group compared to the IgG OS. In glutamate metabolism, GLUD1 has been associated with neurodegenerative properties in neuronal tissues [68, 69], as GLUD1 can stimulate the Krebs cycle, resulting in increased oxidative phosphorylation and ROS production, in turn, is detrimental to RGCs [70]. Therefore, the lower abundance of GLUD1 in the DNM1L OS group of our study suggested reduced cellular stress by ROS due to anti-DNM1L Ab injection. In summary, our study demonstrated that anti-DNM1L-Ab injection affected DNM1L expression and phosphorylation status at Ser635 and Ser656. In addition, mitochondrial proteins were found significantly altered in the DNM1L OS group, which could indicate altered mitochondrial biogenesis. However, these proteins do not appear to interact with DNM1L directly but rather result from altered DNM1L expression or phosphorylation state. DNM1L regulates not only the mitochondrial division but also mitochondrial distribution. In this process, DNM1L interacts with the cytoskeleton or cytoskeleton-associated proteins, including MAP1A, TPPP, and COTL1, which were significantly differentially expressed between both study groups. MAP1A and the TPPPs were more abundant in the DNM1L OS group compared to IgG OS, indicating an increased MT polymerization, stabilization, and extension of the MT network [71].