Targeted Microglial Attenuation through Dendrimer–Drug Conjugates Improves Glaucoma Neuroprotection

Pitha, Ian; Kambhampati, Siva P.; Sharma, Anjali; Sharma, Rishi; McCrea, Liam; Mozzer, Ann; Kannan, Rangaramanujam M.

doi:10.1021/acs.biomac.2c01381

Cited by 8 publications

(5 citation statements)

References 64 publications

(122 reference statements)

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Section: Nanotechnologymentioning

confidence: 99%

“…Studies have found that slow release of GDNF and CNTF with nanotechnology can extend the duration of efficacy and significantly improve RGC survival in animal glaucoma models [109–112]. Nanomedicine has also improved delivery of antioxidant compounds used to treat glaucoma [113–116,117 ▪ ,118 ▪ ] and delivery of stem cells to the TM [119]. Nanotechnology could meaningfully improve the effectiveness of glaucoma treatment by improving the pharmacologic characteristics of drugs.…”

Section: Nanotechnologymentioning

confidence: 99%

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Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Ciociola,

Fernandez,

Kaufmann

et al. 2023

Current Opinion in Ophthalmology

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Purpose of review The aim of this article is to summarize current research on novel gene, stem cell, neuroprotective, nanomedicine, and vascular therapies for glaucoma. Recent findings Gene therapy using viral vectors and siRNA have been shown to reduce intraocular pressure by altering outflow and production of aqueous humor, to reduce postsurgical fibrosis with few adverse effects, and to increase retinal ganglion cell (RGC) survival in animal studies. Stem cells may treat glaucoma by replacing or stimulating proliferation of trabecular meshwork cells, thus restoring outflow facility. Stem cells can also serve a neuroprotective effect by differentiating into RGCs or preventing RGC loss via secretion of growth factors. Other developing neuroprotective glaucoma treatments which can prevent RGC death include nicotinamide, the NT-501 implant which secretes ciliary neurotrophic factor, and a Fas-L inhibitor which are now being tested in clinical trials. Recent studies on vascular therapy for glaucoma have focused on the ability of Rho Kinase inhibitors and dronabinol to increase ocular blood flow. Summary Many novel stem cell, gene, neuroprotective, nanomedicine, and vascular therapies have shown promise in preclinical studies, but further clinical trials are needed to demonstrate safety and efficacy in human glaucomatous eyes. Although likely many years off, future glaucoma therapy may take a multifaceted approach.

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Section: Nanotechnologymentioning

confidence: 99%

Section: Nanotechnologymentioning

confidence: 99%

Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Ciociola,

Fernandez,

Kaufmann

et al. 2023

Current Opinion in Ophthalmology

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“…For instance, D-NAC functionalized with triphenylphosphonium (TPP) can be incorporated with mitochondrial targeting ability, which enables D-NAC to localized selectively into the mitochondria of activated microglia/macrophages and attenuates neuroinflammation after systemic administration in a rabbit TBI model. [156] Since dendrimers can potentially be modified into a diagnostic agent for real-time visualization in vivo, [151,157] this suggested that it may be possible to develop D-NAC into a theranostic agent for TBI. [136] Copyright 2023, John Wiley & Sons, Inc.…”

Section: Dendrimer For Immunotherapymentioning

confidence: 99%

Multifunctional Nanoparticles and Nanoclusters as a Theranostics and Symptoms Disappearing Agent for Traumatic Brain Injury

Zoey,

Ghosh,

Palanivel

et al. 2023

Advanced NanoBiomed Research

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Traumatic brain injury (TBI) is one of the most common causes of disability and mortality worldwide, creating a large socioeconomic burden annually. Secondary injury physiopathology is known to play a prominent role in exacerbating neurodegeneration post‐TBI and is potentially preventable by therapies. However, due to the heterogeneity of TBI and the complexity of the pathological mechanisms that ensue, there are currently no effective disease‐modifying treatments to prevent TBI‐associated disability and mortality. Nanotechnology has emerged in recent decades as a promising platform for the development of multifunctional neuroprotective agents for TBI. Herein, current multifunctional innovations are explored in this review in nanotechnology, which target the secondary injury pathological mechanisms of TBI and show promise in improving future post‐TBI management. Also, potential new directions for the future development of TBI treatment are discussed.

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“…Ameboid-activated microglia and elevated expression of proinflammatory cytokines in postmortem glaucoma eyes have been reported [ 2 , 6 ]. Activated and proliferative microglia have been noted in the optic nerve and retina of experimental glaucoma animal models in the early stages of the disease, before RGC and axon loss [ 7 , 8 ]. Activated microglia can help clear cellular debris and secrete neuroprotective factors; however, with chronic persistent activation, their activation become irreversible and trigger secondary retinal and optic nerve damage.…”

Section: Introductionmentioning

confidence: 99%

“…Activated microglia can help clear cellular debris and secrete neuroprotective factors; however, with chronic persistent activation, their activation become irreversible and trigger secondary retinal and optic nerve damage. By modifying microglial activation, depleting microglia, and blocking microglial downstream, targeting microglia delays neurodegenerative processes in glaucoma animals [ 7 – 10 ]. Taken together, previous studies suggest the potential treatment strategies to target microglia in glaucoma.…”

Section: Introductionmentioning

confidence: 99%

Human adipose tissue-derived stem cell extracellular vesicles attenuate ocular hypertension-induced retinal ganglion cell damage by inhibiting microglia- TLR4/MAPK/NF-κB proinflammatory cascade signaling

Ji,

Peng,

Liu

et al. 2024

acta neuropathol commun

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Microglia-mediated neuroinflammatory responses are recognized as a predominant factor during high intraocular pressure (IOP)-induced retinal and optic nerve injury along with potential therapeutic targets for the disease. Our previous research indicated that mesenchymal stem cell (MSC) treatment could reduce high IOP-induced neuroinflammatory responses through the TLR4 pathway in a rat model without apparent cell replacement and differentiation, suggesting that the anti-neuroinflammatory properties of MSCs are potentially mediated by paracrine signaling. This study aimed to evaluate the anti-neuroinflammatory effect of human adipose tissue-derived extracellular vesicles (ADSC-EVs) in microbead-induced ocular hypertension (OHT) animals and to explore the underlying mechanism since extracellular vesicles (EVs) are the primary transporters for cell secretory action. The anti-neuroinflammatory effect of ADSC-EVs on LPS-stimulated BV-2 cells in vitro and OHT-induced retinal and optic nerve injury in vivo was investigated. According to the in vitro research, ADSC-EV treatment reduced LPS-induced microglial activation and the TLR4/NF-κB proinflammatory cascade response axis in BV-2 cells, such as CD68, iNOS, TNF-α, IL-6, and IL-1β, TLR4, p-38 MAPK, NF-κB. According to the in vivo data, intravitreal injection of ADSC-EVs promoted RGC survival and function, reduced microglial activation, microglial-derived neuroinflammatory responses, and TLR4/MAPK/NF-κB proinflammatory cascade response axis in the OHT mice. Our findings provide preliminary evidence for the RGC protective and microglia-associated neuroinflammatory reduction effects of ADSC-EVs by inhibiting the TLR4/MAPK/NF-κB proinflammatory cascade response in OHT mice, indicating the therapeutic potential ADSC-EVs or adjunctive therapy for glaucoma.

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Targeted Microglial Attenuation through Dendrimer–Drug Conjugates Improves Glaucoma Neuroprotection

Cited by 8 publications

References 64 publications

Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Multifunctional Nanoparticles and Nanoclusters as a Theranostics and Symptoms Disappearing Agent for Traumatic Brain Injury

Human adipose tissue-derived stem cell extracellular vesicles attenuate ocular hypertension-induced retinal ganglion cell damage by inhibiting microglia- TLR4/MAPK/NF-κB proinflammatory cascade signaling

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