HSP 27 has been reported to interact with cytoskeletal proteins. It is hypothesized that the accumulation of these proteins after ischemia may have an important role in the stabilization of cytoskeletal structures and/or their recovery from disruption. Ischemia reperfusion leads to a disruption of actin microfilaments,
65,66 which are found in the cytoplasm of cells. Ischemia can lead to redistribution of actin throughout the cytoplasm,
67 potentially causing increased antiactin antibodies. An increased level of antiactin antibodies was detected in this study (
Fig. 5). An increase of systemic antibody reactivity against HSPs, especially against HSP 27, was also apparent in our study (
Fig. 5). Ischemic retinas also showed an increase in HSP 27–positive RGCs
68 and expression of HSP 27 is known to be increased after retinal ischemia,
68,69 occurring in both neuronal and nonneuronal retinal cells and even after cerebral ischemia.
70 These studies indicate that a similar ischemic induction of stress-related proteins might occur in retinas. Yokoyama et al.
71 demonstrated that resistance of RGCs to ischemia/reperfusion injury is enhanced by electrical application of HSP 27 protein solution into the vitreous immediately after the ischemic event. The authors explicate that, through this technique, HSP 27 proteins are able to enter and protect RGCs, given that they are considered to have a neuroprotective function.
72 Both HSP 27 and HSP 70 are inhibitors of apoptotic cell death.
73 HSP 27 can maintain both the redox homeostasis and mitochondrial stability of cells. It is capable of binding to both proteins, cytochrome c, after its release from mitochondria, and procaspase-3, preventing the formation of apoptosome complexes.
74,75 HSP 27 is also capable of blocking Daxx (death-associated protein 6)-mediated apoptosis. Daxx directly binds to the death domain of Fas, a widely expressed cell death receptor.
76 Possibly the increase of antibodies against HSPs we detected in our animals could be an indicator for the loss of necessary tissue protection through ischemia/reperfusion damage. Better understanding of the role of the immune system in postretinal ischemia events may in the future create novel and innovative therapeutic approaches.