视神经损伤
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Figure 1｜Effects of intravitreal S100B injection on retina and optic nerve.
Effect of intravitreal S100B application on retina and optic nerve: In the next step, S100B was injected intravitreally to examine not only the influence of systemic immunization but also the local effects of ocular antigens. For this purpose, 14 and 21 days after intravitreal S100B injection, evaluations were carried out (Figure 1A). We noted that the RGC number as well as the β-III tubulin protein level was reduced in the S100B animals. Moreover, active apoptotic mechanisms could be detected 14 days after immunization. The optic nerve neurofilament structure was damaged starting 3 days after immunization (Figure 1B). Based on these findings we assume that S100B directly damages the optic nerve axons and consequently, RGC cell bodies degenerate (Kuehn et al., 2018).
In a follow-up project our research group, an increased rate of NfκB, a transcription factor that regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses, was observed in RGCs 14 days after S100B injection. Retinae in the S100B group displayed almost twice as many nuclear factor kappa-light-chain-enhancer of activated B+ (NfκB) cells as both control groups (both: P = 0.04; Figure 1B). This indicates that NfκB activation might be associated with neuronal degeneration in this model. In the same study, an increased concentration of interleukin (IL)-1β was detected in serum of S100B animals after 14 days and also a tendency towards an IL-1β increase was detected in the aqueous humor. In addition, a highly increased number of retinal microglia expressing IL-1β could be noted in S100B retinae at 14 days. More precisely, significantly more IL-1β expressing microglia were observed in the S100B group in comparison to the PBS (P = 0.01) and the na?ve group (P = 0.02). Furthermore, the number of microglia as well as the number of active microglia was increased in the retina and the optic nerve at 14 days. A strong microglia response was especially noted in optic nerves of S100B animals. The number of microglia, labelled with an anti-Iba1 antibody via immunohistology, was more than two-fold higher in the optic nerves of the S100B group than in the na?ve and the PBS control groups (both: P < 0.001). Active microglia were visualized with a double staining of ED1+ and Iba1+ cells. Interestingly, the number of active microglia was much higher in the S100B group than in the controls (both: P < 0.001). Later on, after 21 days, microglia numbers as well as the rate of active microglia in both tissues were comparable within the groups (Figure 1B). Furthermore, the macroglia in retinae and optic nerves were analyzed after intravitreal S100B injection. Neither at 14 nor at 21 days, any differences regarding the occurrence of macroglia were observed between the retinae of the different groups. In contrast, in the optic nerve a slight astrogliosis, via glial fibrillary acidic protein (GFAP) staining, was detected in the S100B group in comparison to the na?ve group after 14 days (P = 0.03), where differences in the GFAP area were not seen between the S100B optic nerves and the ones of the PBS group.
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