stilbenes and Ocular-Hypertension

To explore the roles of mitochondrial biogenesis and dynamics in both RGC-5 cells apoptosis and rat retinal damage induced by elevated pressure and their involvement in resveratrol (RSV)-induced cell protection.. The chronic ocular hypertension (COH) model was established in rats by injecting superparamagnetic iron oxide into anterior chamber. The RGC-5 cells were incubated under ambient and elevated pressure (70 mm Hg) respectively. The intraocular pressure (IOP) was measured using a handheld Tonolab tonometer; mitochondrial dysfunction was analyzed by membrane potential (MMP) depolarization, reactive oxygen species (ROS) level and transmission electron microscope (TEM) detection. Annexin V/PI staining and the terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay were performed for apoptosis detection. Hematoxylin-Eosin staining was performed for retinal morphology detection. The expression of mitochondrial biogenesis and dynamics relating proteins were analyzed by western blot.. The retinal morphology and mitochondrial function deteriorated in chronic ocular hypertension (COH) rats. The cells showed apoptosis and mitochondrial dysfunction under elevated pressure (70 mm Hg) incubation. Upregulating AMPK, NRF-1, Tfam, mfn-2, OPA1 expression with RSV-treatment could decrease the cell apoptosis, mitochondrial membrane potential depolarization, ROS generation both in in vitro and in vivo experiments, and normalized the retinal morphology in vivo.. Both in vitro and in vivo experiments demonstrated that activated AMPK/PGC-1α signaling pathway and improved expression of proteins were related to mitochondrial dynamics could be the possible mechanism underlying in the RSV's mitochondrial protection.

Topics: Animals; Antioxidants; Apoptosis; Cell Line, Tumor; Cell Survival; Intraocular Pressure; Male; Mitochondria; Mitochondrial Diseases; Ocular Hypertension; Organelle Biogenesis; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resveratrol; Retina; Stilbenes

Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.

Topics: Administration, Topical; Animals; Antioxidants; Aqueous Humor; Cell Count; Disease Models, Animal; Female; Glucocorticoids; Intraocular Pressure; Male; Matrix Metalloproteinase 2; Ocular Hypertension; Ophthalmic Solutions; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Sprague-Dawley; Resveratrol; Retina; Retinal Ganglion Cells; Stilbenes; Tonometry, Ocular; Trabecular Meshwork

To study the effects of ocular hypertension (OHT) on the visual system of C57BL/6 pigmented mice, the limbal and episcleral veins of the left eye were laser photocoagulated (LP). LP increased the intraocular pressure during the first five days (d), reaching basal values at 7d. To investigate the effect of OHT on the retinal ganglion cell (RGC) retrograde axonal transport, hydroxistilbamidine methanesulfonate (OHSt) was applied to both superior colliculi (SCi) and the retinas were dissected 2 or 4 weeks after LP. To determine RGC survival, these same retinas were immunoreacted against Brn3a (general RGC population) and melanopsin (intrinsically photosensitive RGCs, m+RGCs). To study whether OHT affected non-RGC neurons in the ganglion cell layer (GCL), RGCs were immunodetected with Brn3a and all GCL nuclei counterstained with DAPI in a group of animals examined 4 weeks post-LP. Innervation of the SCi was examined at 10 days, 8 or 14 weeks after LP with the orthogradely transported cholera toxin subunit-B. OHT resulted in diffuse and sectorial loss of OHSt+RGCs (50% at 2 weeks and 62% at 4 weeks) and in a comparable loss of Brn3a+RGCs at the same time intervals. m+RGCs decreased to 59% at 2 weeks and to 46% at 4 weeks, such loss was diffuse, did not parallel the sectorial loss of the general RGC population and was more severe in the superior-temporal retina. In the GCL, cell loss is selective for RGCs and does not affect other non-RGC neurons. The retinotectal innervation appeared significantly reduced at 10 days (55.7%) and did not progress further up to 14 weeks (46.6%). Thus, LP-induced OHT results in retrograde degeneration of RGCs and m+RGCs, as well as in the loss of CTB-labelled retinotectal terminals.

Topics: Animals; Cell Count; Indoles; Intraocular Pressure; Light Coagulation; Male; Mice, Inbred C57BL; Neurons, Afferent; Ocular Hypertension; Pigmentation; Retinal Degeneration; Retinal Ganglion Cells; Rod Opsins; Stilbenes; Superior Colliculi; Transcription Factor Brn-3A; Visual Pathways