Protective effect of ultrasound microbubble combined with gross saponins of <i>tribulus terrestris</i> on glaucomatous optic nerve damage

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Abstract

Background

To investigate the protective effect of ultrasound microbubble combined with gross saponins of tribulus terrestris (GSTT) (a Chinese herb) on glaucomatous optic nerve damage.

Methods

Rabbits were randomly divided into five groups. Normal (Group A), high intraocular pressure (IOP, Group B), GSTT (Group C), GSTT + ultrasound (Group D), and GSTT + ultrasound + microbubble destruction (Group E). The high intraocular pressure eye (model eye) was compared to the normal eye (control eye) at 1, 2, and 4 weeks after model establishment. Rabbits were sacrificed 4 weeks later to measure the retina thickness using Cirrus OCT, slit lamp photograph, and fundus photography. The retina and optic nerve of rabbits in each group were collected and the stretched retina were prepared for retinal ganglion cell (RGC) counting, the optic nerve axon was measured, and a transmission electron microscopy was used.

Results

Retina thickness based on Cirrus OCT: mean retinal thickness in Group E was significantly greater than that in Group B, but still thinner than that in Group A. RGCs counts: RGCs counts in Group E were significantly higher than those in Groups B, C, and D but still lower than those in Group A. Quantitative analysis of optic nerve axons: In Group E, the number of optic nerves was increased, diameters of optic nerve axons were decreased, the percentage of optic nerve area occupied by axons was increased, and there were statistically significant differences compared to Groups B, C, and D. Content of GSTT in retina: The content of GSTT in Group E was significantly higher than that in other groups. Observation of the rabbit optic nerves: In Group E, the structure of the myelin sheath of the optic nerve was still intact but less ordered, and the microtubule and microfilament structures in the axons were clear.

Conclusions

Combination of the ultrasound microbubble and GSTT can improve the protective effect of GSTT on optic nerve damage in rabbits with ocular hypertension.

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Most cited references 19

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Drug and gene delivery across the blood-brain barrier with focused ultrasound.

Kelsie F Timbie, Brian Mead, Richard Price (2015)

The blood-brain barrier (BBB) remains one of the most significant limitations to treatments of central nervous system (CNS) disorders including brain tumors, neurodegenerative diseases and psychiatric disorders. It is now well-established that focused ultrasound (FUS) in conjunction with contrast agent microbubbles may be used to non-invasively and temporarily disrupt the BBB, allowing localized delivery of systemically administered therapeutic agents as large as 100nm in size to the CNS. Importantly, recent technological advances now permit FUS application through the intact human skull, obviating the need for invasive and risky surgical procedures. When used in combination with magnetic resonance imaging, FUS may be applied precisely to pre-selected CNS targets. Indeed, FUS devices capable of sub-millimeter precision are currently in several clinical trials. FUS mediated BBB disruption has the potential to fundamentally change how CNS diseases are treated, unlocking potential for combinatorial treatments with nanotechnology, markedly increasing the efficacy of existing therapeutics that otherwise do not cross the BBB effectively, and permitting safe repeated treatments. This article comprehensively reviews recent studies on the targeted delivery of therapeutics into the CNS with FUS and offers perspectives on the future of this technology.

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Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer's disease

Yanan Liu, Youcong Gong, Wenjie Xie … (2020)

The delivery of drugs across the blood–brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases. The delivery of drugs across the blood–brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases. In this work, we constructed a nano-system using microbubbles to promote the crossing of drugs across the BBB, where microbubbles in combination with focused ultrasound were used to mediate the transient opening of the BBB and delivery of nanomedicines. This system (Qc@SNPs-MB) was formed by embedding quercetin-modified sulfur nanoparticles (Qc@SNPs) in microbubbles (MB). Qc@SNPs-MB was destroyed instantly when exposed to ultrasonic pulses, and it enhanced the permeability of the blood vessels, resulting in the brief opening of the BBB owing to the “sonoporation” effect. Also, Qc@SNPs were released from the outer shell of the microbubbles and entered the brain across the open BBB, accumulating in the brain parenchyma. Due to the rapid accumulation of Qc@SNPs in the brain, it effectively reduced neuronal apoptosis, inflammatory response, calcium homeostasis imbalance, and oxidative stress, which are all mediated by endoplasmic reticulum stress, and protected nerve cells, thus treating Alzheimer's disease (AD) effectively. The Morris water maze experiment showed that the learning ability and memory ability of the AD mice treated with Qc@SNPs were significantly improved, and no obvious side effects were found. Therefore, Qc@SNPs-MB combined with ultrasound can provide an effective and safe drug delivery method for the treatment of neurodegenerative diseases and a promising strategy for endoplasmic reticulum stress therapy.

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Ultrasound-responsive neurotrophic factor-loaded microbubble- liposome complex: Preclinical investigation for Parkinson's disease treatment

Chung-Yin Lin, Yu-Chien Lin, Ching-Yun Huang … (2020)

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Author and article information

Journal

Journal ID (nlm-ta): Ann Transl Med

Journal ID (iso-abbrev): Ann Transl Med

Journal ID (publisher-id): ATM

Title: Annals of Translational Medicine

Publisher: AME Publishing Company

ISSN (Print): 2305-5839

ISSN (Electronic): 2305-5847

Publication date (Print and electronic): September 2021

Publication date (Print): September 2021

Volume: 9

Issue: 18

Electronic Location Identifier: 1436

Affiliations

[1 ]deptDepartment of Glaucoma, Shenzhen Eye Hospital, Shenzhen Eye Hospital Affiliated with Jinan University, School of Optometry , Shenzhen University , Shenzhen, China;

[2 ]Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology) , Shenzhen, China

Author notes

Contributions: (I) Conception and design: X Shen, J Guo; (II) Administrative support: Q Li, J Wang; (III) Provision of study materials or patients: N Fan; (IV) Collection and assembly of data: M Lai; (V) Data analysis and interpretation: L Huang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Qiang Li. Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China. Email: gemmyleon@ 123456163.com ; Jiantao Wang. Shenzhen Eye Hospital, Shenzhen Eye Hospital Affiliated with Jinan University, School of Optometry, Shenzhen University, Shenzhen 518040, China. Email: wangjiantao65@ 123456126.com .

Article

Publisher ID: atm-09-18-1436

DOI: 10.21037/atm-21-4230

PMC ID: 8506763

PubMed ID: 34733988

SO-VID: 01a29576-ed76-4622-9143-5a16e883acc8

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

Protective effect of ultrasound microbubble combined with gross saponins of tribulus terrestris on glaucomatous optic nerve damage

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Abstract

Background

Methods

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Conclusions

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NeuroImaging Methods

Most cited references 19

Drug and gene delivery across the blood-brain barrier with focused ultrasound.

Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer's disease

Ultrasound-responsive neurotrophic factor-loaded microbubble- liposome complex: Preclinical investigation for Parkinson's disease treatment

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