advertisement
Abstract #82639 Published in IGR 20-4
Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma
Huang S; Huang P; Yu H; Lin Z; Liu X; Shen X; Guo L; Zhong YInvestigative Ophthalmology and Visual Science 2019; 60: 4346-4359
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.
Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai, China.
Full articleClassification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
