Neuroprotection for Age-Related Macular Degeneration

Lin, Jonathan B.; Murakami, Yusuke; Miller, Joan W.; Vavvas, Demetrios G.

doi:10.1016/j.xops.2022.100192

Cited by 24 publications

(6 citation statements)

References 110 publications

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“…The quest for effective treatments to prevent visual loss from chronic progressive retinopathies necessitates the development of robust neuroprotective strategies. These strategies have the potential to halt photoreceptor death, thus averting subsequent vision loss [ 30 , 51 ]. Drawing insights from the neuroprotective activities of 3K3A-APC in the brain and CNS [ 11 , 15 , 16 , 17 ] and recognizing the retina, particularly the macula, as an extension of the brain, we propose 3K3A-APC as a potential neuroprotective treatment for AMD and other neurodegenerative retinal pathologies.…”

Section: Discussionmentioning

confidence: 99%

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina

Weinberger

Budnik

Nisgav

et al. 2023

IJMS

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3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.

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Section: Discussionmentioning

confidence: 99%

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina

Weinberger

Budnik

Nisgav

et al. 2023

IJMS

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“…Neuroprotection involves the use of therapeutic agents to enhance neuronal endurance by protecting the anatomical and physiological features of the neurons. The neuroprotective agents in AMD are very important along with other therapeutic strategies for slowing down the progression and preventing the loss of vision [ 62 , 63 ]. Elamipretide, a tetrapeptide-based agent, is effective in decreasing oxidative stress and mitochondrial dysfunction, thereby controlling the disease progression [ 64 ].…”

Section: Current Approaches For the Treatment Of Amdmentioning

confidence: 99%

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

Paliwal

Prajapati

Srichana

et al. 2023

Life

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The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD.

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“…At baseline, there was a mean area of geographic atrophy of 7.73 mmin all groups, which increased to 7.99 at 6 months and 10.98 m mat 30 months. A final readout for the trial has not yet been reported [19].…”

Section: Targeting Inflammationmentioning

confidence: 99%

Novel oral medications for retinal disease: an update on clinical development

DeBoer

Agrawal²,

Rahimy

2023

Current Opinion in Ophthalmology

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Purpose of reviewIntravitreal and periocular injections for retinal disease provide a targeted delivery of medication to the eye. However, given risks of injections, including endophthalmitis, pain and treatment burden for both patients and retina specialists, there has been significant interest and effort in developing oral medications for the management of retinal disease. This article provides clinical and preclinical details of new oral medications in the pipeline for management of retinal disease. Recent findingsSeveral new oral medications show clinical and preclinical promise for the management of retinal disease, including macular degeneration, diabetic retinopathy and Stargardt disease. SummaryOral medications provide promise for treating retinal disease, possibly increasing compliance, and reducing side effects of intravitreal or periocular injections. However, difficulties in this approach include systemic side effects and efficacy targeting the eye. There are multiple medications that are currently under investigation with the potential to act as stand-alone treatment or as an adjunct treatment for management of retinal diseases such as diabetic retinopathy, macular degeneration and Stargardt disease.

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Neuroprotection for Age-Related Macular Degeneration

Cited by 24 publications

References 110 publications

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

Novel oral medications for retinal disease: an update on clinical development

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