In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1.

BACKGROUND: Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. METHODS: The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 µM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver-Burk plots to characterize the specific inhibition model and kinetic parameters. RESULTS: Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 µM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 µM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 µM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 µM- 1 and the Kinact value of 0.0515 min- 1. CONCLUSIONS: The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis.

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

How curcumin affects hyperglycemia-induced optic nerve damage: A short review.

Considered to be one of the most important non-contagious systemic diseases worldwide, diabetes mellitus is still a topical issue on the health agenda with the problems it causes. Exposure to long-term hyperglycemia causes diabetic complications (diabetic neuropathy, nephropathy and retinopathy). The optic nerve can suffer damage by both diabetic retinopathy and neuropathy during diabetes, both because it is formed by axons of retinal ganglion cells and these axons belong to the central nervous system. The issue of hyperglycemia on the optic nerve have been described as diabetic papillopathy, posterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy and optic atrophy in clinical studies. Experimental studies indicated axon-myelin degeneration in addition to microvascular and ultrastructural changes caused by the hyperglycemia-induced optic nerve damage. Although there are several proposed biochemical mechanisms to cause these damages, oxidative stress emerges as an important factor among them. Oxidative stress leads to pathological state on the nerve cells by affecting the DNA, protein and lipids at different levels. These are causing deterioration on nerve conduction velocity, myelin sheath and nerve structure, neurotrophic support system, glial cells and nerve function. Curcumin, as an important antioxidant, can be an ideal prophylactic agent to eliminate damages on optic nerve. Curcumin helps to regulate the balance of antioxidant and reactive oxygen species by targeting various molecules (NF-κB, STAT3, MAPK, Mfn2, Nrf2, pro-inflammatory cytokines). In addition, it shows healing or preventive effects on myelin sheath damage via regulating ferritin protein in oligodendrocytes. It is also effective in preventing neurovascular damage.

Potentially blinding adverse drug reaction to peribulbar lignocaine anesthesia: A rare case report.

Peribulbar lignocaine anesthesia is commonly used in ophthalmic surgeries. It rarely causes any severe allergic reaction. A 63-year-old male presented with complicated pseudophakia. He underwent successful vitrectomy under local anesthesia. He later presented with acute-onset proptosis, orbital swelling, and extraocular movement restriction. He was afebrile with normal blood workup and radiological investigations and gave a similar past history. The patient was treated successfully with intravenous medications but two months later developed optic atrophy. An adverse reaction to lignocaine appears to be the most probable cause. Early detection and prompt management of this condition may avert a potentially grave visual outcome. Literature review shows that this case is one of its kinds to report this potentially blinding complication of peribulbar lignocaine anesthesia.

Effects of adenosine triphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation.

PURPOSE: Acute methanol exposure leads to systemic intoxication and toxic optic neuropathy. In this experimental study, we aimed to determine the protective effects of intravenous administration of ATP in methanol-induced optic neuropathy. MATERIALS AND METHODS: A total of 18 male albino Wistar rats weighing between 267 and 282 g were used for the experiment. The animals were divided into three groups as healthy control (HC), methanol (M), and methanol + ATP (M-ATP) groups. Distilled water was given to the healthy control group (n = 6) as the solvent, while 20% methanol was administered orally to the rats in M (n = 6) and M-ATP (n = 6) groups at a dose of 3 g/kg. Four hours after the administration of 20% methanol orally to the M-ATP group, ATP was injected intraperitoneally at a dose of 4 mg/kg. Eight hours after ATP injection, the animals were sacrificed by high-dose (50 mg/kg) thiopental anaesthesia and biochemical and histopathological examinations were performed on the removed optic nerve tissues. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS) and total anti-oxidant status (TAS) were analysed with biochemical tests. RESULTS: MDA, TOS and OSI were significantly higher and tGSH and TAS levels were significantly lower in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). There was not any significant difference between healthy controls and M-ATP group regarding the oxidative stress parameters. There was a significant destruction and increase in thickness and astrocyte numbers and edema-vacuolization in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). CONCLUSION: Intravenous ATP administration had a significant positive effect on the oxidative stress parameters and optic nerve structure in methanol-intoxicated rats. Antioxidant therapies should be considered in future studies as a possible therapy for methanol-induced toxic optic neuropathy.

The Intraocular Pressure-Lowering Effect of Persimmon leaves (Diospyros kaki) in a Mouse Model of Glaucoma.

The aim of this study was to evaluate the pharmacological efficacy of persimmon leaves in two glaucoma models, microbeads-induced ocular hypertension (OHT) and DBA/2 mouse. Thus, we demonstrated that Ethanol Extract of Diospyros kaki (EEDK) reduced elevated intraocular pressure (IOP) in both mouse models of glaucoma by measurements with a tonometer. In particular, we revealed that retinal ganglion cell loss and optic nerve damage caused by IOP elevation were markedly diminished as assessed by TUNEL assay, H&E staining, and fluorescent staining, while the expression of soluble guanylate cyclase (sGCα-1) increased, when EEDK was administered, as revealed by western blot. Moreover, the b-wave magnitude indicating functional scotopic vision was significantly improved in EEDK-administered DBA/2 mice during the 10-week follow-up study, as observed with electroretinography. Collectively, our results suggested that EEDK could be an effective therapeutic and IOP-lowering agent for preventing and treating retinal degenerative diseases such as glaucoma.

Clinical analysis of severe visual loss caused by inhalational methanol poisoning in a chronic process with acute onset:a retrospective clinical analysis.

BACKGROUND: To analyze the clinical features and prognosis of the visual loss resulted from inhalational methanol poisoning in 8 Chinese patients. METHODS: Eight consecutive patients seen at the Beijing Tongren Hospital of Capital Medical University, Beijing, China between January 2003 to August 2017, with complains of vision loss in both eyes, identified as inhalational methanol poisoning. Detailed medical history was extracted. All patients underwent optic nerve and brain magnetic resonance imaging (MRI) scan, laboratory tests, and visual function analysis. Treatment protocols were large dosage of methylprednisolone and B vitamins over 3 months. Patients were seen at 3-month intervals until a year. RESULTS: Eight patients with optic neuropathy caused by inhalation toxicity of methanol were under observation, whose methanol-contact time spans were form 4 days to 5 years for occupational exposure. All the patients had acute onset, transient systemic symptoms on early stage, both eyes involved with severe visual impairment (visual acuity 0.1 or even worse). Retrobulbar optic nerves (ONs) were the major sites involved. Optic nerve MRI scan showed increased signal of bilateral ONs in the orbit and the canal parts, with enhancement. After treatment, the visual function of these patients got improved in different degree in a year follow-up, but not satisfactorily. CONCLUSIONS: Inhalational methanol toxicity may lead to serious damage to ON in a process of chronic intoxication with acute attack, and with poor prognosis.

Carvone protects against paclitaxel-induced retinal and optic nerve cytotoxicity: a histopathological study.

Purpose: Carvone (CVN) is a natural monoterpene found in essential oils of many aromatic plant species. In this study, we investigated the protective effect of CVN against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats. Methods: Twenty-four male adult Wistar albino rats (250-400 g) were randomized into four equal groups comprising six animals in each. Group 1 (control group) received intraperitoneal (i.p.) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received i.p. CVN [(S)-(+)- CVN, (5S)-5-Isopropenyl-2-methyl-2-cyclohexen-1-one, C10H14, 25 mg/kg], while Group 3 received i.p. PTX (5 mg/kg) weekly for 4 weeks. Group 4 received i.p. CVN (25 mg/kg) 30 min after i.p. PTX (5 mg/kg) weekly for 4 weeks. At the end of the experimental period, retinal and optic nerve tissues were evaluated histopathologically. Results: All retinal specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated increased retinal vascularity and rosette-like structures in the outer nuclear layer, while in PTX-CVN group all eyes (6/6) demonstrated normal retinal vascularity and absence of rosette-like structures. All optic nerve specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated severe vacuolization and decrease in the number of astrocytes and oligodendrocytes, while 3 eyes (3/6) demonstrated marked single cell necrosis. In PTX-CVN group, 4 eyes (4/6) demonstrated moderate vacuolization while, 2 eyes (2/6) had none. Compared with PTX group, 1 eye (1/6) in PTX-CVN group demonstrated a decrease in numbers of astrocytes and oligodendrocytes while 5 eyes (5/6) were normal. No remarkable single cell necrosis was observed in PTX-CVN group. Conclusions: Our histopathological findings demonstrated the potential protective role of CVN against PTX-induced retinal and optic nerve cytotoxicity. CVN might be a promising molecule in counteracting oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders.

Oculohypotensive effects of various acetozolamide nanopreparations for topical treatment of animal model-induced glaucoma and their impact on optic nerve.

Acetozolamide-ACZ, carbonic anhydrase inhibitor- is still the most effective systemic drug for glaucoma treatment. Due to its limited ocular bioavailability, topical formulations are not available yet. This study introduces within the framework of nanotechnology three nanopreparations of acetozolamide for topical application, one of them is liposomal phospholipid vehicle and the other two preparations are propolis and Punica granatum (pomegranate). The hypotensive effect of these different nanopreparations in lowering the increased intraocular pressure that was induced in experimental rabbits is monitored for 130 hrs. Structural characteristics of the optic nerve dissected from all involved groups were studied by Fourier transfrom infrared spectroscopy. The obtained results indicate the impact of the topically applied acetozolamide nanopreparations in lowering the intraocular pressure to its normotensive control value. On the other hand, the optic nerve characteristics were found to be dependent on the way acetozolamide introduced. Glaucoma affects structural components that contain OH group and increases ß-turns of the protein secondary structure while, reducing the content of both α-helix and Turns. In the same context, liposomal-acetozolamide and propolis nanopreparations protecting the optic nerve protein secondary structure from these changes associated with glaucoma.

Further Evidence on Efficacy of Diet Supplementation with Fatty Acids in Ocular Pathologies: Insights from the EAE Model of Optic Neuritis.

In the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis, we recently demonstrated that diet supplementation with a balanced mixture of fatty acids (FAs), including omega 3 and omega 6, efficiently limited inflammatory events in the retina and prevented retinal ganglion cell (RGC) death, although mechanisms underlying the efficacy of FAs were to be elucidated. Whether FAs effectiveness was accompanied by efficient rescue of demyelinating events in the optic nerve was also unresolved. Finally, the possibility that RGC rescue might result in ameliorated visual performance remained to be investigated. Here, the EAE model of optic neuritis was used to investigate mechanisms underlying the anti-inflammatory effects of FAs, including their potential efficacy on macrophage polarization. In addition, we determined how FAs-induced rescue of RGC degeneration was related to optic nerve histopathology by performing ultrastructural morphometric analysis with transmission electron microscopy. Finally, RGC rescue was correlated with visual performance by recording photopic electroretinogram, an efficient methodology to unravel the role of RGCs in the generation of electroretinographic waves. We conclude that the ameliorative effects of FAs were dependent on a predominant anti-inflammatory action including a role on promoting the shift of macrophages from the inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This would finally result in restored optic nerve histopathology and ameliorated visual performance. These findings can now offer new perspectives for implementing our knowledge on the effectiveness of diet supplementation in counteracting optic neuritis and suggest the importance of FAs as possible adjuvants in therapies against inflammatory diseases of the eye.

Preconditioning with carbon monoxide inhalation promotes retinal ganglion cell survival against optic nerve crush via inhibition of the apoptotic pathway.

Optic neurodegeneration, in addition to central nervous trauma, initiates impairments to neurons resulting in retinal ganglion cell (RGC) damage. Carbon monoxide (CO) has been observed to elicit neuroprotection in various experimental models. The present study investigated the potential retinal neuroprotection of preconditioning with CO inhalation in a rat model of optic nerve crush (ONC). Adult male Sprague­Dawley rats were preconditioned with inhaled CO (250 ppm) or air for 1 h prior to ONC. Animals were euthanized at 1 or 2 weeks following surgery. RGC densities were quantified by hematoxylin and eosin (H&E) staining and FluoroGold labeling. Visual function was measured via flash visual evoked potentials (FVEP). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and caspase­9 and caspase­3 activity in the retinas, were assessed at 2 weeks post­ONC. The RGC density of CO + crush rats was significantly increased compared with that of the corresponding crush­only rats at 2 weeks (survival rate, 66.2 vs. 48.2% as demonstrated by H&E staining, P<0.01; and 67.6 vs. 37.6% as demonstrated by FluoroGold labeling, P<0.05). FVEP measures indicated a significantly better­preserved latency and amplitude of the P1 wave in the CO + crush rats compared with the crush­only rats. The TUNEL assays demonstrated fewer apoptotic cells in the CO + crush group compared with the crush­only group, accompanied by the suppression of caspase­9 and caspase­3 activity. The results of the present study suggested that inhaled CO preconditioning may be neuroprotective against ONC insult via inhibition of neuronal apoptosis.

Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis.

AIMS: Optic neuritis (ON) is an inflammatory disease of the optic nerve, which often occurs in patients with multiple sclerosis (MS) and leads to retinal ganglion cell (RGC) death and even severe visual loss. Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects. Here, we examined the effects of VPA in experimental autoimmune encephalomyelitis (EAE) rats and explored the underlying mechanisms. MAIN METHODS: EAE was induced by subcutaneous injection with myelin basic protein, emulsified with complete Freund's adjuvant and Mycobacterium tuberculosis H37Ra into the Lewis rats. Subsequently, animals in the VPA groups were treated orally with VPA (250 or 500 mg/kg) once a day for 13 days. KEY FINDINGS: VPA treatment significantly attenuated inflammation and microgliosis in optic nerve in EAE-ON rats, as evidenced by the decrease in the mRNA levels of interferon (INF)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-17, and inducible nitric oxide synthase (iNOS), the suppression in nuclear factor (NF)-κB signal pathway as well as the down-regulation of CD11b expression in optic nerve. Additionally, the apoptotic RGCs were remarkably increased in the EAE retina, which was inhibited by VPA treatment. Consistent with the TUNEL staining, VPA administration also obviously suppressed the ratio of Bax: Bcl-2 and the expression of cleaved caspase-3 and PARP in optic nerve in EAE rats. SIGNIFICANCE: Our findings demonstrated that VPA treatment could prevent inflammation responses and RGC apoptosis in optic nerve in EAE-ON rats, suggesting that VPA may be available for optic nerve protection during ON.

Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia-reperfusion injury model treated with sildenafil citrate.

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia-reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (n = 6) and two experimentally induced ischaemia-reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia-reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet® ). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT-PCR for expression of Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. Sildenafil-treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo-treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase-7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase-6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro-apoptotic factors and decrease in the anti-apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in SG similar to the controls.

Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

Purpose: The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). Methods: The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Results: Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. Conclusions: The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina.

Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients. The purpose of the present study was to examine the potential neuroprotective effect of Mg acetyltaurate (MgAT) on RGC death induced by NMDA. MgAT was proposed mainly due to the combination of magnesium (Mg) and taurine which may provide neuroprotection by dual mechanisms of action, i.e., inhibition of NMDA receptors and antioxidant effects. Rats were divided into 5 groups and were given intravitreal injections. Group 1 (PBS group) was injected with vehicle; group 2 (NMDA group) was injected with NMDA while groups 3 (pre-), 4 (co-), and 5 (post-) treatments were injected with MgAT, 24 h before, in combination or 24 h after NMDA injection respectively. NMDA and MgAT were injected in PBS at doses 160 and 320 nmol, respectively. Seven days after intravitreal injection, the histological changes in the retina were evaluated using hematoxylin & eosin (H&E) staining. Optic nerves were dissected and stained in Toluidine blue for grading on morphological neurodegenerative changes. The extent of apoptosis in retinal tissue was assessed by TUNEL assay and caspase-3 immunohistochemistry staining. The estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors and caspase-3 activity in retina was done using enzyme-linked immunosorbent assay (ELISA) technique. The retinal morphometry showed reduced thickness of ganglion cell layer (GCL) and reduction in the number of retinal cells in GCL in NMDA group compared to the MgAT-treated groups. TUNEL and caspase-3 staining showed increased number of apoptotic cells in inner retina. The results were further corroborated by the estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors, and caspase-3 activity in retina. In conclusion, current study revealed that intravitreal MgAT prevents retinal and optic nerve damage induced by NMDA. Overall, our data demonstrated that the pretreatment with MgAT was more effective than co- and posttreatment. This protective effect of MgAT against NMDA-induced retinal cell apoptosis could be attributed to the reduction of retinal oxidative stress and activation of BDNF-related neuroprotective mechanisms.

Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush.

Chronic neuro-inflammation is involved in the death of retinal ganglion cells (RGCs) in glaucoma. The aim of this study is to determine whether wogonin can suppress inflammatory responses and rescue RGCs death after optic nerve crush (ONC), an ideal animal model of glaucoma. Wogonin was administered intraperitoneally 10 min after establishment of ONC model. In this study, wogonin treatment reduced RGCs loss and inhibited RGCs apoptosis demonstrated by the increased Brn3a labeling RGCs at day 14 and the decreased cleaved caspase-3 expression at day 7 after ONC, respectively. In ONC model, number of GFAP-positive glial cells and iba1-positive microglial cells were increased, combined of the elevated level of pro-inflammatory cytokines released in retina at day 7. However, most of these responses were inhibited after wogonin treatment. The level of TLR4 expression, NF-κB-P65 nucleus location and NF-κB-P65 phosphorylation were increased in retina at day 1 after ONC, which was significantly reduced after wogonin treatment. These results demonstrated that wogonin protected RGCs survival and suppressed neuro-inflammation in retina after ONC by inhibiting TLR4-NF-κB pathways. We conclude that wogonin could be a possible strategy for the treatment of glaucoma.

Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a common rodent model for multiple sclerosis (MS). Yet, the long-term consequences for retina and optic nerve (ON) are unknown. C57BL/6 mice were immunized with an encephalitogenic peptide (MOG35-55) and the controls received the carriers or PBS. Clinical symptoms started at day 8, peaked at day 14, and were prevalent until day 60. They correlated with infiltration and demyelination of the ON. In MOG-immunized animals more microglia cells in the ONs and retinas were detected at day 60. Additionally, retinal ganglion cell (RGC) loss was combined with an increased macroglia response. At this late stage, an increased number of microglia was associated with axonal damage in the ON and in the retina with RGC loss. Whether glial activation contributes to repair mechanisms or adversely affects the number of RGCs is currently unclear.

Ultrasound-guided ophthalmic regional anesthesia.

PURPOSE OF REVIEW: Needle-based and cannula-based eye blocks are 'blind' techniques prone to rare but serious complications. Ultrasound, an established adjunct for peripheral nerve block, may be beneficial for ophthalmic anesthesia application. The present review details the evolution of ultrasound-guided eye blocks, outlines safety issues, and reviews recent studies and editorial opinions. RECENT FINDINGS: Ultrasound-assisted ophthalmic regional anesthesia allows imaging of key structures such as the globe, orbit, and optic nerve. Recent findings reveal that needle path is not reliably predictable by clinical evaluation. Needle tips are frequently found to be intraconal, extraconal, or transfixed in the muscle cone independent of the intended type of block. In addition, contemporary human and animal studies confirm that real-time observation of local anesthetic spread inside of the muscle cone correlates directly with block success. SUMMARY: Ultrasound-guided ophthalmic regional anesthesia is evolving beyond simple visualization of the anatomy. Recent research emphasizes the imprecision of needle tip location without ultrasound and the key role of imaging local anesthetic dispersion. There is ongoing debate in the literature regarding the utility of routine ultrasound for eye blocks.

Quantitative Assessment of Optic Nerve Changes in Patients With Diabetic Macular Edema Treated With Fluocinolone Acetonide Vitreous Implants.

BACKGROUND AND OBJECTIVE: To evaluate glaucomatous changes in patients with diabetic macular edema (DME) treated with intravitreal implants releasing 0.2 µg/day or 0.5 µg/day fluocinolone acetonide (FAc) (Iluvien 0.2 µg/day; Alimera Sciences, Alpharetta, GA) or sham control. PATIENTS AND METHODS: Fundus photographs were assessed to determine clinically significant changes in glaucomatous indicators. RESULTS: The mean cup-to-disc ratio (CDR) change was similar with all three treatments. Compared with sham control, a significantly greater proportion of patients treated with 0.5 µg/day but not 0.2 µg/day FAc experienced a CDR increase of greater than 0.1. There was no significant increase in the proportion of patients experiencing a CDR increase of greater than 0.2 with either dose of implant versus sham control. Other indicators of glaucomatous change did not differ significantly with treatment. Subgroup analyses showed no differences in cupping based on ocular or baseline characteristics. CONCLUSION: Treatment with FAc for 36 months was not associated with significant glaucomatous optic nerve head changes in patients with DME with or without increased intraocular pressure. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:418-425.].

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.