## 3 Discussion
In an experimental autophagy model, down-regulation of ATP6V1A led to neurodegeneration, defective lysosomal function, and autophagy arrest, which increased the vulnerability of RGCs [107]. Since ATP6V1A expression was up-regulated in the DNM1L OS group in our study, this seems to play a neuroprotective role. Exocytosis of synaptic vesicles, containing neurotransmitters, occurs by SV2A and SV2B, among others [108, 109, 110, 111], maintaining neuronal communication between pre- and post-synapses [112]. SV2A was up-regulated in the DNM1L OS group compared to the IgG OS in our study. Low expression or dysfunction of SV2A has been shown to initiate neurodegenerative processes, including neuronal apoptosis, axon damage, and synapse loss, in AD and ocular hypertension [113, 114]. Therefore, increased SV2A abundance may indicate increased exocytosis and thus enhanced neuronal activity. Although the presented study showed a new approach for an IOP independent glaucoma therapy, some study limitations should be pointed out. Different animal models may emphasize signal transduction pathways differently. Therefore, a single model cannot reflect all features of a multifactorial disease such as glaucoma. Because of limited tissue amounts, this study focused on analyzing the target protein, DNM1L, certain phosphorylation, and mitochondrial apoptosis-related proteins. For the analysis of proteomic changes in retinal tissues with minimal tissue usage, mass spectrometric analysis was performed. Our study demonstrated that EVO altered DNM1L phosphorylation status at Ser635 and Ser656, which indicates a higher fusion rate than the division rate in the IgG OS group. Abnormally high fusion of mitochondria results in hyper elongated mitochondria and has been described as a feature of senescent cells [115, 116]. The senescence of retinal cells after stress induction has been previously reported as a reversible state to prevent death [31]. Based on the data of our study, we propose that anti-DNM1L Ab injection altered the phosphorylation status, possibly by blocking the phosphorylation site at Ser656, such that cells could return from a senescent state to a biologically active state. This, in turn, could trigger increased mitochondrial division, leading to increased synthesis of DNM1L, as shown by western blot. Consequently, a stabilization of the cytoskeleton could occur since, by mass spectrometry, cytoskeleton stabilizing proteins were found to be significantly increased in the DNM1L OS group and could lead to an increased survival of RGCs. In the study of mitochondrial dynamics, fission and fusion are crucial processes as well as biogenesis, i.e., the synthesis of mitochondrial proteins. Therefore, it is also important to see the proteomic changes concerning the total mitochondrial content. Interestingly, we detected by mass spectrometry proteins of the mitochondrial cytochrome reductase complex (cytochrome b-c1 complex subunit 1, mitochondrial (UQCRC2), cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2)) which were not significantly altered in the IgG OS or DNM1L OS, suggesting that the total mitochondrial content seems unaltered by the treatment. The hypotheses put forward in this manuscript are based on the functional properties of the identified proteins as published in other studies and disease models such as PD or Alzheimer's disease. For concrete evidence of altered mitochondrial dynamics and mitochondrial distribution further studies need to be conducted with this focus, for example, by electron microscopy. Nevertheless, these results highlight the protective effect of anti-DNM1L-Ab injection and provide clues to the molecular background worth pursuing further, opening new options for potential glaucoma therapy.