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International Ophthalmology

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01-07-2020 | Glaucoma | Original Paper

Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats

Authors: Liang Liang, Liye He, Mengnan Zhu, Baoji Chen, Changyi Xiao

Published in: International Ophthalmology | Issue 7/2020

Abstract

Objective

To observe the protective effects of carnosic acid on rat retinal ganglion cells (RGCs) among acute ocular hypertension rats.

Methods

Sixty male SPF (specific-pathogen-free) SD rats (10 weeks) were randomly assigned to untreated group, carnosic-acid-treated group and hypertensive group with 20 rats for each. The acute ocular hypertension animal model was induced by the perfusion of normal saline solution into anterior chamber of eyes to elevate the intraocular pressure (IOP) to 110 mmHg for 60 min in the rats of the carnosic-acid-treated group and hypertensive group. Then, the carnosic acid dissolving in dimethyl sulfoxide (DMSO) was intraperitoneally injected for consecutive 7 days in the carnosic-acid-treated group, and only DMSO was used in the same way in the hypertensive group. The rats were killed 2 weeks after experiment, and retinal sections were prepared for histopathological and apoptotic retinal ganglion cells (RGCs) examination by hemotoxylin and eosin staining and TUNEL staining. Use immunofluorescence employed to examine the survival of RGCs. This study protocol was approved by the Ethic Committee for Experimental Animal of Three Gorges University.

Results

The retinal morphology and structure were clear in the untreated group. The edema of retinal tissue, loosely arranged RGCs and swollen nucleus were seen in the hypertensive group. In the carnosic-acid-treated group, the retinal morphology and structure were regular. The retinal nerve fiber layer (RNFL) thickness was (32.96 ± 1.63), (58.96 ± 1.57) and (50.11 ± 2.37) μm, and the apoptotic cell number was (6.92 ± 2.96), (29.85 ± 6.40) and (14.69 ± 2.98)/field, and the survived cell number was (2363.17 ± 148.45), (1308.67 ± 106.02) and (1614.17 ± 96.39)/0.235 mm² in the untreated group, hypertensive group and carnosic-acid-treated group, respectively, showing significant differences among groups (F = 339.284, 81.583, 122.68, all at P < 0.01). Compared with the untreated group, the RNFL thickness was thickened, the number of apoptotic RGCs was much more, and the number of survived RGCs was decreased in the hypertensive group. In the carnosic-acid-treated group, the RNFL thickness was thinner, the number of apoptotic RGCs was reduced, and the number of survived RGCs was increased in comparison with the untreated group (all at P < 0.01).

Conclusions

Carnosic acid plays a protective effect on RGCs by inhibiting the cell apoptosis in acute ocular hypertension rats.

Varma R, Lee PP, Goldberg I et al (2011) An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol 152(4):515–522. https://doi.org/10.1016/j.ajo.2011.06.004 CrossRefPubMedPubMedCentral

Pinazo-Durán MD, Zanón-Moreno V, Gallego-Pinazo R et al (2015) Oxidative stress and mitochondrial failure in the pathogenesis of glaucoma neurodegeneration. Prog Brain Res 220:127–153. https://doi.org/10.1016/bs.pbr.2015.06.001 CrossRefPubMed

Xia TJ, Bi LW, Zhao ZD et al (2015) Antioxidant activity and antibacterial activity of carnosic acid. Nat Prod Res Dev 27(01):35–40

Xiang QS, Meng X, Qiao Y et al (2013) Effect of carnosic acid on free radical-mediated oxidative damage to proteins. Food Sci 34(15):281–284. https://doi.org/10.7506/spkx1002-6630-201315058 CrossRef

Maruoka H, Sasaya H, Sugihara K et al (2011) Low-molecular-weight compounds having neurotrophic activity in cultured PC12 cells and neurons. J Biochem 150(5):473–475. https://doi.org/10.1093/jb/mvr113 CrossRefPubMed

Tai J, Cheung S, Wu M et al (2012) Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine 19(5):436–443. https://doi.org/10.1016/j.phymed.2011.12.012 CrossRefPubMed

Rezaie T, McKercher SR, Kosaka K et al (2012) Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration. Invest Ophthalmol Vis Sci 53(12):7847–7854. https://doi.org/10.1167/iovs.12-10793 CrossRefPubMedPubMedCentral

The Advanced Glaucoma Intervention Study (AGIS) (2000) 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 130(4):429–440CrossRef

Handy DE, Loscalzo J (2012) Redox regulation of mitochondrial function. Antioxid Redox Signal 16(11):1323–1367CrossRef

10.

Trinei M, Migliaccio E, Bernardi P et al (2013) p66Shc, mitochondria, and the generation of reactive oxygen species. Methods Enzymol 528:99–110. https://doi.org/10.1016/B978-0-12-405881-1.00006-9 CrossRefPubMed

11.

Namekata K, Kimura A, Kawamura K et al (2013) Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma. Cell Death Differ 20(9):1250–1256. https://doi.org/10.1038/cdd.2013.91 CrossRefPubMedPubMedCentral

12.

Pinazo-Durán MD, Gallego-Pinazo R, García-Medina JJ et al (2014) Oxidative stress and its downstream signaling in aging eyes. Clin Interv Aging 9:637–652. https://doi.org/10.2147/CIA.S52662 CrossRefPubMedPubMedCentral

13.

Galbis-Estrada C, Pons-Vázquez S, Gallego-Pinazo R et al (2012) Glutathione-dependent formaldehyde dehydrogenase (ADH3) and low km mitochondrial aldehyde dehydrogenase (ALDH2). New evidence for differential expression in the rat retina in response to oxidative stress. Free Radic Res 46(1):77–84. https://doi.org/10.3109/10715762.2011.640324 CrossRefPubMed

14.

Jing W, Weiyan H, Lanchun Z et al (2016) Study on the protective effect on neurons damaged by H₂O₂ and stability of carnosic acid. Pharmacol Clin Chin Mater Med 32(2):43–46. https://doi.org/10.13412/j.cnki.zyyl.2016.02.013 CrossRef

15.

Weiyan H, Haofei Y, Rangping Z (2014) Protective effect of carnosic acid on β-amyloid protein induced hippocampal neuron injury. Nat Prod Res Dev 4:490–493. https://doi.org/10.16333/j.1001-6880.2014.04.010 CrossRef

16.

Zhang D, Lee B, Nutter A et al (2015) Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid. J Neurochem 133(6):898–908. https://doi.org/10.1111/jnc.13074 CrossRefPubMedPubMedCentral

17.

Yesil-Celiktas O, Sevimli C, Bedir E et al (2010) Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines. Plant Foods Hum Nutr 65(2):158–163. https://doi.org/10.1007/s11130-010-0166-4 CrossRefPubMed

18.

Goldblum D, Mittag T (2002) Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye. Vis Res 42(4):471–478CrossRef

19.

Unoki K, LaVail MM (1994) Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor. Invest Ophthalmol Vis Sci 35(3):907–915PubMed

20.

Kara S, Gencer B, Karaca T et al (2014) Protective effect of hesperetin and naringenin against apoptosis in ischemia/reperfusion-induced retinal injury in rats. Sci World J 2014:797824CrossRef

21.

Jia L, Haofei Y, Rongping Z, Weiyan H et al (2018) Stability of acetylated carnosic acid and its protective effect on hippocampal neurons. Pharmacol Clin Chin Mater Med 34(3):30–32. https://doi.org/10.13412/j.cnki.zyyl.2018.03.008 CrossRef

22.

Birtić S, Dussort P, Pierre FX, Bily AC, Roller M (2015) Carnosic acid. Phytochemistry 115:9–19CrossRef

Title: Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats
Authors: Liang Liang
Liye He
Mengnan Zhu
Baoji Chen
Changyi Xiao
Publication date: 01-07-2020
Publisher: Springer Netherlands
Keywords: Glaucoma
Hypertension
Hypertension
Published in: International Ophthalmology / Issue 7/2020
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-020-01359-8

At a glance: The STEP trials

Springer Medicine

Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats

Abstract

Objective

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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