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VIEW · 2025 · IF 8.5

Harmonizing NAD+ metabolism with CeMOF nanozyme to orchestrate intraocular pressure modulation for glaucoma treatment

Youjia Zhang,Ming Chen,Yi Tian,Bo Qin,Xiaoxiao Chen,Yiwen Zhou,Jinhai Huang,Mei Yang,Xinghuai Sun,Yuan Lei,Yuhong Chen

Elevated intraocular pressure (IOP) is a critical risk factor for the development and progression of glaucoma. However, current treatments focus primarily on mechanical stress relief, neglecting the underlying issue of diminished cellular energy production in patients. In this study, we investigated the impact of NAD + reduction on IOP regulation and explored the potential of NAD + precursors as a therapeutic strategy. We investigated the role of NAD + metabolism in glaucoma and revealed decreased nicotinamide phosphoribosyltransferase (NAMPT) expression in both patients and the human trabecular meshwork (HTM) cell model. Supplementation with NAD + precursors, nicotinamide (NAM) or nicotinamide mononucleotide (NMN), provided protective effects in H 2 O 2 -treated HTM cells and reduced IOP in ocular hypertension mouse models by mitigating senescence, extracellular matrix accumulation, and oxidative stress. To optimize drug delivery, we engineered the NAM@CeMOF-2 nanozyme system, which achieved a maximum IOP reduction in Cav1 ⁻/⁻ mice following 7 days of treatment. This localized treatment improved bioavailability and reduced systemic side effects. These findings suggest that NAD + deficiency plays a role in glaucoma development and propose novel therapeutic targets for addressing cellular dysfunction in glaucoma.

研究领域: 医学 · 生物化学 · 眼科研究
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ACS Nano · 2025 · IF 16

Reproducible Transpalpebral Intraocular Pressure Sensing Enabled by Low-Energy-Barrier Ion Pumping

Xueyang Ren,Xuefei Zhu,Xiaodong Shao,Wen Yang,Yanmei Meng,Shiyu Chen,Yannan Wang,Jianqing Li,Qin Jiang,Benhui Hu

Elevated intraocular pressure (IOP) is a major risk factor for blindness in glaucoma patients, highlighting the critical need for continuous IOP monitoring. While traditional transpalpebral tonometers (TTs) circumvent corneal contact by adopting Goldmann applanation principles through impulsive corneal flattening forces, their measurement accuracy is inherently compromised by eyelid-induced cushion effects. In contrast, parallel-plate capacitive sensors employ constant compressive loading upon the eyelid, achieving palpebral compaction to mitigate the cushion effects. More recently, ion-pump-based capacitive sensors have emerged as promising alternatives, particularly due to their enhanced sensitivity. Nevertheless, these sensors exhibit sharp sensitivity deterioration at extended measurement ranges (0–10 kPa). This operational constraint originates from the strong hydrogen bond energies (between confining matrices and ions) and rigid block copolymer matrices’ steric hindrance. To address these limitations, we developed a transpalpebral tonometer featuring low-energy-barrier ion pumps, incorporating (3-aminopropyl)triethoxysilane (APTES)-silanized liquid metal nanoparticles (LM NPs) as confining matrices and an ionic liquid as an ion donor. The low-energy barrier arises from (1) weaker hydrogen bonds between the N–H of APTES and the F of the ionic liquid and (2) reduced crystallinity in the elastomeric matrices induced by LM NPs. Our sensor achieves a sensitivity of 24.88 kPa–1 with maintained linearity over 0–85 kPa. In vivo animal trials over 120 min validated its continuous IOP monitoring capability, reliably detecting elevated IOP states and demonstrating clinical potential for glaucoma management.

研究领域: 医学工程 · 生物医学
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Regenerative Biomaterials · 2023 · IF 6.7

Sustained release of brimonidine from polydimethylsiloxane-coating silicone rubber implant to reduce intraocular pressure in glaucoma

Huang Chang,Shen Yuening,Zhao Yujin,Zhang Zhutian,Gao Shunxiang,Hong Jiaxu,Xu Jianjiang,Meng Qingtao,Sun Xinghuai,Sun Jianguo

Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit’s conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.

CAS / MDL: 919-30-2
研究领域: 药学 · 生物医学工程 · 眼科
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Intraocular Pressure Monitoring Smart Contact Lens with High Environmental Stability

Huan Yang,Hengtian Zhu,Hanwen Liu,Zhengyi Mao,Junxian Luo,Shugeng Zhu,Zizhong Hu,Songtao Yuan,Fei Xu

Smart contact lenses (SCLs), integrating various functional components, serve as a platform for wirelessly intraocular pressure (IOP) monitoring. Accurate and dynamic measurements offer crucial clinical references for patients with ocular hypertension. Nevertheless, the complex ocular environment poses great challenges, particularly for inductor–capacitor–resistor (LCR) type IOP sensors, which suffer signal instability due to variations of ocular dielectric properties. Here, an innovative IOP monitoring sensor with robust environmental stability, achieved by integrating the ground shield, is proposed. Employing a capacitive pressure sensor with porous polydimethylsiloxane (PDMS) structure encased in a hydrogel, the study successfully demonstrates high-sensitivity monitoring of IOP changes using in vitro porcine eyes. This optimized design empowers the wireless IOP sensor with a sensitivity of 1.15 ‰/mmHg. It exhibits exceptional frequency stability after undergoing 100 wear cycles on ten distinct porcine eyes and remains reliable across a wide range of metabolite concentrations typical of normal eyes. Notably, any observed frequency shift translates into IOP changes within a 3 mmHg range, showcasing its suitability for repeated use and daily IOP monitoring.

CAS / MDL: 50-81-7 56-81-5
研究领域: 生物医学工程 · 眼科 · 传感器与执行器 · 材料科学
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JOURNAL OF MEDICINAL CHEMISTRY · 2025 · IF 6.8

Design, Synthesis, and Evaluation of Novel ROCK Inhibitors for Glaucoma Treatment: Insights into In Vitro and In Vivo Efficacy and Safety

Qiang Li,Cunrui Li,Yuanmin Chang,Mingzhi Su,Rilei Yu,Zhangjian Huang,Yue-Wei Guo,Xin Jin

The inhibition of Rho-associated coiled-coil kinase (ROCK) has emerged as a promising strategy for reducing intraocular pressure (IOP) and treating glaucoma. Here, we report the synthesis and evaluation of novel ROCK inhibitors, D25 and R3, which were designed to optimize selectivity, efficacy, and ocular bioavailability. D25 potently inhibited ROCK1/2 with IC50 values of 47.2 nM and 33.8 nM, respectively, surpassing Netarsudil. Compound R3 had weaker ROCK inhibition but demonstrated favorable lipophilicity (logP) and good selectivity to ROCKs, which enhances its potential and safety for ocular delivery. In human trabecular meshwork (HTM) cells, R3 showed lower cytotoxicity than Netarsudil and effectively mitigated oxidative damage, enhanced cellular integrity, and reduced inflammatory cytokine secretion. In rabbit models, D25 significantly lowered IOP, outperforming (S)-Netarsudil. R3 exhibited weaker IOP-lowering efficacy but better selectivity. D25 is a promising glaucoma treatment candidate, with R3 as a safer alternative for further optimization.

研究领域: 药理学 · 眼科 · 分子生物学
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ACS Sensors · 2023 · IF 8.9

Contact Lens Sensor with Anti-jamming Capability and High Sensitivity for Intraocular Pressure Monitoring

Xueyang Ren,Yunfan Zhou,Fangzhou Lu,Leili Zhai,Hao Wu,Zhongda Chen,Changxian Wang,Xuefei Zhu,Yandong Xie,Pingqiang Cai,Juan Xu,Xianglong Tang,Jianqing Li,Jin Yao,Qin Jiang,Benhui Hu

Contact lens sensors provide a noninvasive approach for intraocular pressure (IOP) monitoring in patients with glaucoma. Accurate measurement of this imperceptible pressure variation requires highly sensitive sensors in the absence of simultaneously amplifying IOP signal and blinking-induced noise. However, current noise-reduction methods rely on external filter circuits, which thicken contact lenses and reduce signal quality. Here, we introduce a contact lens strain sensor with an anti-jamming ability by utilizing a self-lubricating layer to reduce the coefficient of friction (COF) to remove the interference from the tangential force. The sensor achieves exceptionally high sensitivity due to the strain concentration layout and the confined occurrence of sympatric microcracks. The animal tests prove our lens can accurately detect IOP safely and reliably.

研究领域: 医学工程 · 生物医学
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Active trans-corneal drug delivery with ocular adhesive micelles for efficient glaucoma therapy

Qiuyu Wei,Chenchen Zhu,Guiping Yuan,Jiahui Jin,Jing Zhang,Wufa Fan,Ying Piao,Shiqun Shao,Sen Lin,Jiajia Xiang,Youqing Shen

Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)- block -poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.

研究领域: 药剂学 · 眼科 · 药物递送系统
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Journal of Healthcare Engineering · 2022 ·Vol. 2022 ·期 1 ·2271937 · IF 3.822

[Retracted] Real-Time Monitoring of Intraocular Pressure in Glaucoma Patients Using Wearable Mobile Medicine Devices

Xiangwen Yuan,Jiabin Zhang

Glaucoma is caused by excessive aqueous humor in the eye, resulting in a continuous or intermittent increase of intraocular pressure, which exceeds the tolerance of the eyeball and damages the optic nerve. Existing treatments for glaucoma do not work well or have significant side effects. Intraocular pressure signal is a very important physiological signal that needs real-time and accurate monitoring in glaucoma patients, especially in severe glaucoma patients. Therefore, long-term, real-time, and accurate monitoring of intraocular pressure is of great significance for the diagnosis and treatment of glaucoma patients. The use of wearable devices for real-time ocular diagnosis and treatment of glaucoma patients is an effective approach. However, the current commonly used intraocular pressure measurement and monitoring technology is difficult to meet the diagnosis and monitoring needs of glaucoma patients in terms of size, measurement accuracy, power consumption, and intelligence. Therefore, facing the needs of glaucoma disease treatment, this topic studies an implantable flexible intraocular pressure sensor for long-term continuous monitoring of intraocular pressure in glaucoma patients and mainly focuses on the working principle, structural design, process fabrication, measurement and control system, characterization, and performance test of the intraocular pressure sensor. It is of great significance for personalized and accurate treatment of glaucoma patients.

研究领域: 眼科 · 生物医学工程 · 传感器技术 · 转化医学 · 慢性病管理
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-15 · IF 14.7

CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice

Yao Mingyu,Zeng Zhenhai,Li Siheng,Zou Zhilin,Chen Zhongxing,Chen Xinyi,Gao Qingyi,Zhao Guoli,Chen Aodong,Li Zheng,Wang Yiran,Ning Rui,McAlinden Colm,Zhou Xingtao,Huang Jinhai

Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2 , as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2 , or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

研究领域: 分子生物学 · 遗传学 · 眼科学 · 神经科学
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 15 ·3335-3345 · IF 6.331

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy

Chen Tan,Fan Jia,Peng Zhang,Xinghuai Sun,Yunsheng Qiao,Xueli Chen,Youxiang Wang,Junyi Chen,Yuan Lei

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine–polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.

CAS / MDL: 27072-45-3 298-93-1
研究领域: 药学 · 纳米技术 · 眼科 · 分子生物学
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MOLECULAR MEDICINE · 2023 ·Vol. 29 ·期 1 ·1-17 · IF 5.7

Long noncoding RNA uc007nnj.1 mediates neuronal death induced by retinal ischemia/reperfusion in mice via the miR-155-5p/Tle4 axis

Feng Yuqing,Lu Jinfang,Peng Xujun,Ge Yanni,Zhang Ran,Li Huiling

Background Retinal ganglion cells (RGCs) apoptosis is a vital manifestation of retinal ischemia/reperfusion (I/R) injury, yet the underlying mechanisms are not well understood. The contribution of long noncoding RNAs (lncRNAs) to this cellular process is currently being explored. Based on a lncRNA chip assay, we aimed to investigate the role of lncRNA uc007nnj.1 in the pathological process of ischemia-induced RGCs apoptosis.Methods Hank’s balanced salt solution containing 10 µM antimycin A and 2 µM calcium ionophore for 2 h to construct an ischemic model in RGCs, and elevation of intraocular pressure to 120 mm Hg for 1 h was used to construct a mouse model of retinal I/R injury.Results In this study, lncRNA uc007nnj.1 was highly upregulated in response to I/R injury in RGCs and mouse retinas. In addition, lncRNA uc007nnj.1 knockdown reduced retinal neuronal cell apoptosis in vitro and in vivo and significantly improved retinal function.DiscussionMechanistically, the results demonstrated that lncRNA uc007nnj.1 acts as ceRNA competitively binding miR-155-5p, thereby enhancing the expression levels of Tle4, thus aggravating ischemia-related apoptosis in RGCs.Conclusion sFinally, our study identifies the lncRNA uc007nnj.1/miR-155-5p/Tle4 axis as a potential target for the prevention of I/R-induced retinal neuronal death.

CAS / MDL: 52665-69-7
研究领域: 神经科学 · 分子生物学 · 眼科 · 细胞生物学
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

A novel injectable thermo/photo dual-crosslinking hydrogel based on modified chitosan for fast sealing open globe injury

Peifang Xu,Pengjie Chen,Yiming Sun,Maimaiti Nuliqiman,Yifan Zhou,Jing Cao,Shan Yu,Jun Huang,Juan Ye

Open globe injuries (OGIs) demand immediate attention to prevent further complications and improve vision prognosis. Herein, we developed a thermo/photo dual-crosslinking injectable hydrogel, HBC_m_Arg, for rapidly sealing OGIs in emergency ophthalmic cases. HBC_m_Arg was prepared with arginine and methacrylic anhydride modified hydroxybutyl chitosan (HBC). HBC_m_Arg was initially in liquid form at 25 °C, enabling easy injection at the injury site. After reaching the ocular surface temperature, it underwent reversible heat-induced gelation to achieve in situ transformation. Further, HBC_m_Arg was capable of rapid photocrosslinking under UV light, forming a dual network structure to bolster mechanical strength, thereby facilitating effective OGI closure. Biocompatibility assessments, including in vitro studies with three ocular cell types and in vivo experiments on rabbit eyes, confirmed the safety profile of HBC_m_Arg. Ex vivo and in vivo burst pressure tests demonstrated the hydrogel's ability to promptly restore intraocular pressure and withstand elevated pressures, underscoring its potential for OGI stabilization. Additionally, the suitable degradation of HBC_m_Arg within ocular tissues, coupled with its stability in ex vivo assessments, presented a delicate balance between stability and biodegradability. In conclusion, HBC_m_Arg holds promise for improving emergency ophthalmic care by providing a rapid, effective, and safe way to seal OGIs in critical situations.

研究领域: 材料科学 · 生物医学工程 · 眼科
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