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.

Effect of pterygopalatine blockade on perioperative stress and inflammatory outcomes following paediatric cataract surgery.

BACKGROUND: General anesthesia is required to perform pediatric cataract surgery. To reduce severity of surgical intervention and postoperative complications, regional techniques have been concomitantly used. The traditional regional ophthalmic techniques are retrobulbar, peribulbar and sub-Tenon blocks, which present some technical difficulties and associated complication risks. The pterygopalatine blockade has been exempt of many of these concerns as it is performed out of the orbit. The purpose of this study was to compare the analgesic and anti-inflammatory effects of the pterygopalatine blockade with retrobulbar block in children undergoing elective congenital cataract surgery. METHODS: After approval of ethics committee and informed consents, patients were enrolled to the study to have either ultrasound-guided pterygopalatine block (group P) or retrobulbar block (group R), with 2 mL lidocaine 2% and 1 mL ropivacaine 0.5%. Hemodynamic monitoring was recorded throughout the perioperative period. Cortisol level and oxidation-reduction status were assessed before and after surgery. Pain and inflammatory response (Tyndall effect, corneal syndrome and edema) were assessed on the first postoperative day. RESULTS: Comparative analysis demonstrated a decrease in cortisol of 123.24% (p˂0.05) and an increase in the redox coefficient of 37.7% (p˂0.05) in group P. Pain intensity was significantly higher in group R until the 16th postoperative hour. The corneal syndrome in patients in group P and group R was noted by 7.6% and in 32.1%, respectively (p˂0.05). CONCLUSION: The use of the pterygopalatine blockade as a component of anesthesia in pediatric cataract surgery allows reduction of the severity of surgical stress during surgical intervention, providing intraoperative hemodynamic stability and prolonged analgesia.

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.

Gypenosides attenuate lipopolysaccharide-induced optic neuritis in rats.

PURPOSE: To evaluate the effect of gypenosides (GPs) on lipopolysaccharide (LPS)-induced optic neuritis rats. METHODS: Optic neuritis was induced by a single microinjection of LPS into the optic nerve of Sprague Dawley rats. GPs (400 mg/kg) was administrated by gavage for 21 days. The optic nerve structure changes and demyelination were observed after hematoxylin & eosin and Luxol-fast blue staining. Apoptosis of retinal ganglion cells (RGCs) was evaluated using Brn3a-TUNEL double staining. Expression of CD68 and glial fibrillary acidic protein (GFAP) were detected using immunofluorescence staining. The mRNA levels of inflammatory factors were measured using quantitative real-time PCR. The protein expression levels in the signal transducer and activator of transcription (STAT) and nuclear factor-κB (NF-κB) pathways were detected using Western blot. RESULTS: GPs treatment prevented the optic nerve structure changes and demyelination in the rats with optic neuritis. GPs treatment downregulated LPS-induced overexpressions of CD68, GFAP and pro-inflammatory factors. GPs treatment inhibited STAT1 and 3 phosphorylation and NF-κB nuclear translocation in the optic nerve and retina of rats with optic neuritis. CONCLUSION: GPs attenuate LPS-induced inflammation, demyelination and optic nerve damage which may be associated with the inhibition of the NF-κB and STAT pathways.

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.

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. METHODS: To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). RESULTS: Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. CONCLUSIONS: The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Calpain inhibition attenuates apoptosis of retinal ganglion cells in acute optic neuritis.

PURPOSE: Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with the pathogenesis of multiple sclerosis (MS) and is initiated by the attack of autoreactive T cells against self-myelin antigens, resulting in demyelination, degeneration of retinal ganglion cells (RGCs), and cumulative visual impairment. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats on day 0, and animals received daily intraperitoneal injections of calpain inhibitor (calpeptin) or vehicle from day 1 until killed. Retinal cell death was analyzed by DNA fragmentation, and surviving ganglion cells were quantified after double labeling of retinal tissue with TUNEL and Brn3a. The expression of apoptotic and inflammatory proteins was determined by Western blotting. RESULTS: It was demonstrated that calpain inhibition downregulates expression of proapoptotic proteins and the proinflammatory molecule nuclear factor-kappa B (NF-κB) in the retina of Lewis rats with acute EAE. Immunofluorescent labeling revealed that apoptotic cells in the RGC layer of vehicle-treated EAE animals were Brn3a positive, and a moderate dose of calpeptin dramatically reduced the frequency of apoptotic RGCs. CONCLUSIONS: These results suggest that calpain inhibition might be a useful supplement to immunomodulatory therapies such as corticosteroids in ON, due to its neuroprotective effect on RGCs.

Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis.

AIM: To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis. MATERIALS AND METHODS: Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up. RESULTS: Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 +/- 0.52 in Group I and 1.52 +/- 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 +/- 0.33 in Group I and 0.36 +/- 0.41 in Group II ( P =0.59). At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits. CONCLUSION: Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.

Optic neuritis with visual field defect--possible Ibuprofen-related toxicity.

OBJECTIVE: To report a case of optic neuritis with visual field defect associated with ibuprofen. CASE SUMMARY: A 41-year-old white man developed blurred vision in his right eye and pain with eye and head movements that lasted 2 days after use of ibuprofen 400 mg 3 times daily during the preceding 3 weeks. Medical and family histories were negative for significant related disease. Ophthalmologic examination revealed a marked decrease in visual acuity to 20/200 in the right eye with quadrant visual field loss and absent responses in visual evoked potential (VEP). After discontinuation of the drug and treatment with high-dose intravenous methylprednisolone and subcutaneous low-molecular-weight heparin, the patient's vision improved to 20/70, the visual field defect vanished, and the VEP returned to almost normal values during a 1 year follow-up period. An objective causality assessment revealed that the adverse reaction was possibly related to ibuprofen. DISCUSSION: Ocular toxicity with blurred vision and centrocecal visual field defects have been rarely associated with long-term ibuprofen intake. We report a case of retrobulbar optic neuritis with quadrant visual field defect following short-term but regular ibuprofen intake. Although idiopathic optic neuritis cannot be completely ruled out, the absence of other risk factors and additional findings plus the improvement after discontinuation of the drug speak for isolated toxic optic neuritis of the right eye. CONCLUSIONS: Drug toxicity is an important differential diagnosis in retrobulbar optic neuritis. Clinicians should be aware of the potential optic toxicity, even with short-term use of a drug, and perform a thorough medication history in every patient with visual disturbances without a clear cause.

[Irrigation therapy as a method of intensive care of ophthalmopathology in the posterior eye segment in children].

Presented in the paper are data of a comparative analysis of efficiency of different methods of administration of drugs in neuritis and partial atrophy of the optic nerve. New techniques of application and fixation of irrigation systems in the retrobulbar and Tenon's space are described. Experimental and clinical data proving advantages of the new method of administration of drugs by an automatic pulse doser in the treatment of inflammatory diseases of the optic nerve are represented. The use of such intensive intermittent technique of administration of drugs in Tenon's space performed at the preliminary stage before electrostimulation of the optic nerve made the procedure by far more effective and ensured better treatment results.

Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway.

Optic neuritis is one of the most common clinical manifestations of multiple sclerosis (MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve (ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.

Homeopathy in Cuban epidemic neuropathy: an open clinical trial.

In an outbreak of epidemic neuropathy (EN) in Cuba (1992-1993), most patients were improved by vitamin therapy. In subjects with residual symptoms, alternative treatments including homeopathy were suggested to ameliorate optic and peripheral signs of the disease. An open clinical pilot trial was conducted on 31 patients with long standing symptoms of optic (OPTI group, n=15) or peripheral EN (PERI group, n=16). During the trial, OPTI and PERI patients continued the same treatment that they received before. Carboneum sulphuratum and Tabacum in homeopathic dilutions were administered for 30 days. These medicines are specific to optic EN, but not closely linked with peripheral EN. Clinical status was evaluated by neurological and ophthalmologic tests at diagnosis (Ddiag), 7 days before homeopathic treatment (D0) and 90 days after (D90). From D0 to D90, the percentages of improvement were 73.3% for the OPTI form and 12.5% for the PERI form. The percentage of improved OPTI patients was significantly higher after the homeopathic treatment vs the period between Ddiag and D0 for optical EN (P<0.01), but not for PERI subjects (P>0.05). In the OPTI group, colour vision, visual acuity and visual field improved after homeopathic treatment (P<0.001), these parameters did not change between Ddiag and D90 (P>0.05). Carboneum sulphuratum and Tabacum showed a reasonable effectiveness in optical EN, but were not effective in PERI EN.

Multicenter clinical trial for evaluating methylprednisolone pulse treatment of idiopathic optic neuritis in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG).

BACKGROUND: A randomized, controlled clinical trial was conducted in 1991 to compare an intravenous megadose of methylprednisolone with a control drug (mecobalamin) for treating acute idiopathic optic neuritis. CASES: Sixty-six cases from 22 clinical centers throughout Japan were examined to evaluate the treatment on visual function parameters, such as visual acuity, visual field, color vision, contrast sensitivity, and critical flicker frequency. OBSERVATIONS: The methylprednisolone pulse treatment group showed faster recovery of visual function, particularly the visual acuity at 1 week (P<.05), Humphrey field analyzer mean deviation at 3 weeks (P<.05), and color vision at 1 week (P<.05). Recovery of contrast sensitivity at several different spatial frequencies was significant in the pulse treatment group at 1 (P<.01), 2 (P<.05), and 4 weeks (P<.05) after the start of treatment. Visual function test results at 12 weeks and 1 year were essentially the same in the two treatment groups. Side effects appeared more frequently in the pulse treatment group than in the control (P<.05). CONCLUSIONS: Pulse treatment does not appear effective for idiopathic optic neuritis even though visual function in the pulse treatment group of this trial recovered more quickly during the initial phase compared to the controls. More effective and specific treatment should be established for optic neuritis.

[Optic neuritis and vitamin C].

Twenty five patients with optic neuritis (ON) of unknown etiology were treated with a high dosage of intravenous vitamin C. We measured blood levels of vitamin A, B1, B2, B6, B12, C, E, folate and zinc. All levels were compared with the normal values of our laboratory. The blood level of vitamin C (p < 0.001) was significantly less than the mean value of the normal. The blood levels of vitamin E, B6 (p < 0.01) and zinc (p < 0.001) also significantly decreased. Intravenous administration of vitamin C was given in those patients with decreased blood level of vitamin C. In order to compare the effect on vision by this treatment, the amplitude of recovery of vision, the time needed to attain the maximum vision, and the speed of visual recovery were analyzed. The results were compared with groups receiving other treatments. That is, Group A received intravenous administration of high dosage of vitamin C, Group B, intravenous pulse administration of corticosterone, Group C, oral administration of corticosterone, and Group D, oral administration of vitamin B12. Vision was significantly improved in all groups. There was no significant difference in improvement of visual acuity. Intravenous administration of vitamin C can be evaluated as the method of choice for the treatment of patients with ON. A possible mode of action by vitamin C on free radicals is discussed.

La ozonoterapia en la neuropatía epidémica forma óptica ¿Beneficio y riesgo? / Ozone therapy in the management of the optic neuritis epidemic. Benefits od risks?

Se realizó un ensayo clínico terapéutico multicéntrico en Ciudad de La Habana, en 576 pacientes afectados de neuropatía epidémica forma óptica, en el período comprendido entre abril de 1993 y febrero de 1994. Se emplearon 11 esquemas de tratamiento, distribuidos aleatoriamente entre los hospitales participantes. Los grupos de tratamiento incluidos fueron : dexametasona, metilprednisolona, hidroxicobalamina+metionina+tiosulfato de sodio, vitaminas, magnetoterapia, ozonoterapia, oxigenación hiperbárica, electroforesis endonasal con vitamina B1, factor de trasnferencia, interferón (INF) alfa natural e interferón alfa 2b recombinante. A todos los pacientes del estudio se les administró vitaminas de base y se consideró a aquéllos tratados con vitaminas sólo como grupo control. La evaluación de los casos se realizó a los 21 días (alta hospitalaria), al mes, 3 y 6 meses, respectivamente. El tratamiento con ozono reflejó diferencias estadísticamente significativas (p<0,05) (en cada uno de los cortes evaluativos efectuados) en cuanto a mejoría y recuperación de los casos tratados con ese proceder. En el resto de los esquemas terapéuticos empleados no se encuentran diferencias significativas. Se evidenció la utilización de las vitaminas

La ozonoterapia en la neuropatía epidémica forma óptica ¿Beneficio y riesgo? / Ozone therapy in the management of the optic neuritis epidemic. Benefits od risks?

Se realizó un ensayo clínico terapéutico multicéntrico en Ciudad de La Habana, en 576 pacientes afectados de neuropatía epidémica forma óptica, en el período comprendido entre abril de 1993 y febrero de 1994. Se emplearon 11 esquemas de tratamiento, distribuidos aleatoriamente entre los hospitales participantes. Los grupos de tratamiento incluidos fueron : dexametasona, metilprednisolona, hidroxicobalamina+metionina+tiosulfato de sodio, vitaminas, magnetoterapia, ozonoterapia, oxigenación hiperbárica, electroforesis endonasal con vitamina B1, factor de trasnferencia, interferón (INF) alfa natural e interferón alfa 2b recombinante. A todos los pacientes del estudio se les administró vitaminas de base y se consideró a aquéllos tratados con vitaminas sólo como grupo control. La evaluación de los casos se realizó a los 21 días (alta hospitalaria), al mes, 3 y 6 meses, respectivamente. El tratamiento con ozono reflejó diferencias estadísticamente significativas (p<0,05) (en cada uno de los cortes evaluativos efectuados) en cuanto a mejoría y recuperación de los casos tratados con ese proceder. En el resto de los esquemas terapéuticos empleados no se encuentran diferencias significativas. Se evidenció la utilización de las vitaminas...

[Early diagnosis and immunocorrective therapy of recurrent facial neuritis as a manifestation of Melkersson-Rosenthal syndrome in adults and children]. / Ranniaia diagnostika i immunokorrigiruiushchaia terapiia retsidivi- ruiushchego nevrita litsevogo nerva kak proiavlenie sindroma Mel'kerssona-Rossolimo-Rozentalia u vzroslykh i detei.

Clinical and immunological examinations of adults and children with Melkersson-Rossolimo-Rosenthal syndrome have revealed immunity deficiency: a decrease of the number of T and B cells, a low immunoglobulin content and the presence of the ++neuro-allergic syndrome according to the increased level of cerebral antibodies. The role of deembiogenetic stigmas in the diagnosis establishment has been demonstrated. The authors suggest the use of immunomodulating therapy including interferogens and immunostimulants of T and B cells (galascorbin and myelopide). Provide evidence for the efficacy of the treatment elaborated.