Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model.

Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions (p < 0.05) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs (p < 0.05). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

BACKGROUND Chronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model. MATERIAL AND METHODS The model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays. RESULTS P1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays. CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma.

Purpose: Glaucoma is a neurodegenerative eye disease characterized by gradually impaired visual field and irreversible blindness due to retinal ganglion cell (RGC) loss. Our previous studies have confirmed that hydrogen sulfide (H2S) takes part in the glaucomatous process and contributes to RGC protection. The present study aimed to further investigate the role of extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway underlying the impact of H2S, to better understand the mechanism through which H2S exerts neuroprotection in glaucoma. Methods: An established rat glaucoma model was used and 168 rats were qualified to undergo sodium hydrosulfide (NaHS, a H2S donor)/PD98059 (an ERK inhibitor) treatment. Then the survival and apoptosis of RGC were evaluated through retrograde labeling and TUNEL staining, along with activity evaluations of ERK 1/2 pathway, intrinsic apoptotic pathway, glial activation, nuclear factor kappa B (NF-κB) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, autophagy, and TNF-α production through immunohistochemistry, Western blotting, and ELISA. Results: The study demonstrated that NaHS suppressed ERK 1/2 pathway activity similarly to PD98059 in retinas of experimental glaucoma rats, while PD98059 also similarly suppressed glial activation, NF-κB pathway, NADPH oxidase, and TNF-α production. However, PD98059 did not affect RGC survival, apoptotic regulation, or autophagy as NaHS did. Conclusions: Our study indicated that inhibition of ERK 1/2 pathway might partly contribute to the neuroprotection by H2S in experimental glaucoma; however, it was insufficient to initiate the therapeutic effect on its own.

A New Terminal Cyano Group-containing Benzodiazepine Alkaloid from the Mangrove Endophytic Fungus Penicillium sp. .

A new benzodiazepine alkaloid containing terminal cyano group has been isolated from a mangrove endophytic fungus, Penicillium 299#. Structure elucidation was determined by 1D and 2D NMR spectroscopy and the absolute configuration was determined by electronic circular dichroism (ECD). The new compound showed no cytotoxic activities in vitro against human cancer lines MDA-MB-435, HepG2, HCT-116, and Calu-3.

Visual field protective effect of Erigeron breviscapus (vant.) Hand. Mazz. extract on glaucoma with controlled intraocular pressure: a randomized, double-blind, clinical trial.

OBJECTIVE: To evaluate the visual field protective effect of Erigeron breviscapus (vant.) Hand. Mazz. (EBHM) extract on glaucoma with controlled intraocular pressure (IOP). METHODS: Forty patients (40 eyes) with primary open-angle glaucoma, visual field defects and a postsurgical IOP of <18 mmHg were enrolled. The EBHM and placebo tablets were given orally according to the randomized and double-blind principle. Two tablets (of either EBHM or placebo) were taken three times a day for a period of 6 months. Patients were examined every 2 months after treatment commenced. At the end of the study, the results were given to the drug manufacturer. RESULTS: All patients completed the prospective, randomized, double-blind, clinical trial. No obvious adverse effects were found in patients during the treatment period. In the placebo group, no significant difference was found in mean defect (MD) or mean sensitivity (MS) between the values at pre-treatment and after 2, 4, and 6 months of treatment. After 6 months of EBHM treatment, the MD was significantly decreased and the MS was significantly increased compared with pre-treatment (p < 0.05). In the patients with moderate and late glaucoma, the MD was significantly decreased and the MS was significantly increased after 2, 4, and 6 months of EBHM treatment compared with pre-treatment. CONCLUSION: EBHM extract may have a partial protective effect on the visual field of glaucoma patients with controlled IOP. Further studies are needed to determine the safety and effectiveness of long-term EBHM treatment.