A potential relevance for OPN in deleterious processes affecting the optic nerve or the D2J retina is suggested from the literature. In several studies, a strong correlation between OPN and different neurodegenerative pathologic conditions, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke, has been described.
50 –56 In these diseases, the degenerations are accompanied by upregulation of OPN either directly at the lesion sites or within the cerebral or spinal fluid. Therefore, OPN is considered a prognostic marker for these diseases or their severity, respectively. Whether OPN is actively involved in the degenerative process or is upregulated during an elicited protective response is not yet completely clarified. However, data have been collected in rodent models of these diseases that argue for a protective but also a degenerative function of OPN, most likely in a context-dependent manner. Meller et al.
56 observed that ventricularly administered OPN significantly reduced the infarct size in a murine model of stroke, emphasizing an active neuroprotective function. In contrast to that, Maetzler et al.
57 found that MPTP-induced neurodegenerations were significantly reduced in OPN
−/− mice, from which the authors concluded an active function for neurodegeneration in Parkinson's disease. There are indications for the ambivalent function of OPN in ocular tissues. Chidlow et al.
58 detected a distinct transient upregulation of OPN within the plexiform layer of rat retinas after excitotoxic and ischemic insults.
58 In patients with Devic's disease, a demyelinating disease affecting the optic nerve, OPN was one of the strongest induced genes, and the authors discussed that it conveys underlying MΦ-mediated inflammation by its chemoattractive capacity.
59 Translated to our findings, it is tempting to speculate that OPN is initially upregulated to counteract deleterious processes such as ischemia, inflammation, or increased IOP and to protect RGCs and optic nerve axons in the D2J model as well. However, if these insults persist or recur frequently, as in glaucoma, this could lead to constant overproduction—thus, local accumulation of OPN—which then could negate the protective effect into the opposite, degenerative, effect. The very preliminary experimental data we present here could be interpreted in a way that supports this hypothesis at least to some extent. Based on the experiments with enucleated D2Rj eyes, and with the admission that this experimental setup is technically not fully developed and leaves room for discussion about the causes for observable disorganization and degeneration, we think one can conclude that the supplementation of medium with 200 ng/mL OPN had an inhibitory or a diminishing effect on cell loss within the GCL compared with the control eyes. Unfortunately, toluidine blue staining is not cell type specific, so we cannot discriminate between RGCs and displaced amacrine cells. Given that both cells are of neuronal origin, one can speculate that OPN, at least at a concentration of 200 ng/mL, might mediate a protective effect for neuronal cells. MTS assays with murine neuronal precursor cells showed that OPN is able to stimulate the metabolic activity of these cells, which could be regarded as an indication that such a hypothetical protective effect of OPN might work by regulating the cell metabolism. Notably, in both experiments, increased concentrations of OPN did not have that protective or stimulatory effect, respectively. This could indicate negation of the positive effects when a certain limiting concentration is exceeded. In any case, it will be left to more sophisticated studies extending our preliminary results to prove a potential protective effect of OPN and perhaps a dose dependency.