Purpose Prostaglandin‐J2 (PGJ2) has been proposed as a potential neuroprotective agent. We wanted to evaluate the toxicity/efficacy of a single intravitreal (IVT) injection of PGJ2 in a rodent model of nonarteritic anterior ischemic optic neuropathy (NAION).
Methods We used the laser‐activated rose Bengal induction method to produce AION in Long‐Evans rats. We evaluated IVT‐PGJ2 retinal and ON toxicity. Following induction, PGJ2 was IVT‐injected in the treatment‐group. IVT phosphate‐buffered‐saline (PBS) was used as control. Functional studies (VEP) were performed at baseline and at 7days post‐treatment. Structural studies included immunohistochemical (IHC), electron microscopic (EM) analysis of the optic nerve (ON), and stereologic analysis of retinal ganglion cell (RGC) numbers at30 day 30.
Results Toxicity: IVT PGJ2 (5 eyes) did not induce any significant functional/structural changes in the retina or ON of treated animals compared with animals injected with PBS (5 eyes) 30 days post‐injection. Efficacy: After a single IVT‐injection, day7 VEPs in the PGJ2‐treatment group (n=7) had amplitudes 103.6% of baseline, whereas the PBS‐treated group (n=6) had VEPs that were 42.4% of the baseline. 30days post‐stroke, EM of ON from the treatment‐group demonstrated significant preservation of axons and decreased demyelination. Stereological RGCcounts confirmed significant (p<0.04) RGC preservation in PGJ2‐treated animals (1462.6 cells/µm2) compared w the stroke+PBS group (1156.5 cells/µm2).
Conclusion A single IVT of PGJ2 preserves RGCs and their axons, and provides sustained neuroprotection for at least 1 month following initial ischemic event.
Purpose The study of meningothelial cells (MCs) and their connection to optic nerve function. MCs line the arachnoid layer of the meninges and form a barrier between the CSF and the blood circulation. A previous study revealed a significantly increased proliferation of MCs in the arachnoid surrounding the optic nerve glaucoma patients.
Methods To explore a possible role of these cells in the pathogenesis of diseases of the optic nerve, we studied the effect of elevated hydrostatic pressure and oxidative stress on MCs using rotenone to inhibit mitochondrial function and compared them to untreated control cells. Cell viability and proliferation were measured using a MTS‐based assay. As a measure of barrier function, we assessed the endocytotic activity of MCs by fluorescence and confocal microscopy following fluorescent‐latex bead uptake.
Results Exposure of MCs to elevated hydrostatic pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. Furthermore, mild oxidative stress severely inhibited endocytosis, thus negatively impacting MC barrier function.
Conclusion MCs surround the optic nerve, thereby shielding it from but also conditioning the microenvironment of this sensitive area. As elevated pressure and oxidative stress occur in patients with increased intracranial pressure who have papilledema and probably in some cases of normal‐tension glaucoma, these phenomena may impact the function of MCs and thus, contribute to the loss of retinal ganglion cells in the course of these and, perhaps, other optic nerve diseases.
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