The choroid plays a key role in preventing retinal damage. We have found an increase in choroidal thickness soon after light damage that is associated with an increased infiltration of leukocytes.
11 However, after 1 week, choroidal thickness decreased. This finding is consistent with findings of past studies indicating that the thinning of the choroid is associated with CD8
+ cytotoxic T lymphocytes infiltrating toward the retina and choroid interface in mice and albino rats.
61,62 This infiltration of T lymphocytes could exert deleterious effects on the choroid, RPE, and retina environments.
61,63 In this study, reduced Cx43 levels were seen as in previous studies, indicating that there is a reduced inflammatory response (the peptide does not in itself reduce Cx43 expression).
11 Furthermore, the hallmarks of retinal stress and upregulation of GFAP in astrocytes and Müller cells (signs of reactive gliosis)
64 were diminished with Cx43MP-NP treatment. It appears that the mimetic peptide reduces the inflammatory process that leads to retinal damage in this model.
11,49 The choroid and retina have resident immune cells and are known to quickly react to invading agents.
65 In fact, accumulating evidence suggests that numerous aberrant macrophages invade the choroid and the retina in light-damaged eyes.
66 We observed increased CD45
+ cells in the choroid, some of them likely to be macrophages. Thus, it is possible that the therapy is regulating specific macrophage cell activity, preventing downstream inflammatory damage. The reduction in CD45
+ leukocytes in the choroid as a result of treatment may be important; interleukin release from these cells may be the cause of increased GFAP expression in Müller cells in an attempt to protect the retina.
67 Sustained release of Cx43MP from NPs works better than the free peptide, suggesting that different/later stages of the inflammatory response may be the target of the therapeutic treatment.