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Purpose. To determine the neuroprotective properties of a latanoprost acid derivative (ACS67) that donates the gas hydrogen sulfide (H(2)S). Methods. Ischemia to the rat retina was induced by elevation of intraocular pressure. Electroretinograms (ERGs) were recorded and the retinas analyzed 2 days later by immunohistochemistry, Western blot analysis, and RT-PCR. Hydrogen peroxide (H(2)O(2)) was used to impose an insult on RGC-5 cells in culture. The nature of the insult to cultures was quantified by the resazurin-reduction assay procedure, staining for reactive oxygen species (ROS) and for apoptosis. ACS67, its sulfurated moiety (ACS1), and latanoprost were tested for both their toxicity and ability to blunt the negative effect of H(2)O(2) on RGC-5 cells. In addition, an assay was used to see whether any of the substances influenced glutathione (GSH) levels in RGC-5 cells. Results. Partial damage to the retina in situ after ischemia was characterized by an alteration of the ERG, a reduction in the retinal localization of specific antigens and a reduction and elevation of defined retinal proteins and mRNAs. Optic nerve axonal proteins were also drastically reduced by ischemia. Most of these changes were significantly blunted by an intravitreal injection of ACS67 directly after ischemia. ACS67, ACS1, and the antioxidant epigallocatechin gallate (EGCG) all stimulated GSH levels and significantly attenuated H(2)O(2)-induced toxicity to RGC-5 cells, whereas latanoprost did not. Conclusions. ACS67 acts as an H(2)S donor through its donating moiety ACS1 and as a consequence is able to act as a neuroprotectant.

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Retinal ganglion cell axons forming the optic nerve (ON) emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina region (ONLR), a transitional area containing a vascular plexus. The ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal ON myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in the age-related disease open angle glaucoma (OAG). We demonstrate that the human and rodent ONLR possesses a mitotically active, age-depletable neural progenitor cell (NPC) niche, with unique characteristics and culture requirements. These NPCs generate both forms of macroglia: astrocytes and oligodendrocytes, and can form neurospheres in culture. Using reporter mice with SOX2-driven, inducible gene expression, we show that ONLR-NPCs generate macroglial cells for the anterior ON. Early ONLR-NPC loss results in regional dysfunction and hypomyelination. In adulthood, ONLR-NPCs may enable glial replacement and remyelination. ONLR-NPC depletion may help explain why ON diseases such as OAG progress in severity during aging.

All subtypes of EP receptors exist primarily in the inner retina at different ages, but their monomer/dimer ratios vary. Stress affects the monomer/dimer ratio and EP2 and EP3 immunoreactivities in Müller cells. Butaprost injected intravitreally significantly blunts the detrimental influence of ischemia/reperfusion to the retina.

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Aims: Deduce whether the isoflavone genistein blunts the effect of ischaemia to the retina. Methods: Ischaemia was induced in rats by raising the intraocular pressure (120 mm Hg) for 50 min. Genistein (10 mg/kg) was injected intraperitoneally 1 h before and after ischaemia. Seven days after ischaemia, the level of mRNAs for neurofilament light (NF-L), caspase 3, caspase 8, glial fibrillary acidic protein (GFAP), poly-ADP ribose polymerase (PARP), Thy-1 and proteins (GFAP, NF-L, PARP) in whole retinas were determined. NF-L and tubulin proteins in optic nerves were also determined. Retinas were also processed for the localization of choline acetyltransferase (ChAT) and GFAP immunoreactivities. Results: Ischaemia caused a significant reduction in ganglion cell proteins in the optic nerve (NF-L and tubulin) and retina (NF-L). Retinal Thy-1 (mRNA and protein) and NF-L (mRNA) were also reduced while mRNAs of caspase 3, caspase 8, PARP and GFAP (also protein) were increased. Changes in the mRNAs and proteins induced by ischaemia were significantly blunted by genistein with the exception of the increase in GFAP and PARP protein/mRNA levels. Ischaemia-induced changes in the localization of ChAT were also clearly attenuated by genistein treatment. Conclusions: Genistein blunts most of the damaging effects caused to the retina by ischaemia.

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