&lt;p&gt;Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration&lt;/p&gt;

Akyol, Engin; Lotery, Andrew

doi:10.2147/btt.s252581

Cited by 19 publications

(19 citation statements)

References 58 publications

(50 reference statements)

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“…Age-related macular degeneration (AMD) is one of the most common back of the eye disorders in the United States [ 1 , 2 , 3 , 4 ]. AMD can cause severe vision impairment and lead to vision loss.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1β and TNF-α after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD.

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Section: Introductionmentioning

confidence: 99%

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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“…Complement activation pathways with genetic variants of complement C3 are strongly associated with the progression of AMD, as complement C3 is a point of convergence for 3 activation pathways (classical, alternative and lectin pathway) [ 210 ]. Complement C3 and its activation products (C3a, C3c and C3d) have been found in basal laminar and linear deposits as well as in surgically removed CNV tissue, which may imply that dysregulation of complement C3 activation plays a particularly significant role in the pathogenesis of AMD [ 211 , 212 ].…”

Section: Therapy Strategies In Amd Targeting the Vasculature And Omentioning

confidence: 99%

Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

Ruan

Jiang

Gericke

2021

IJMS

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Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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“…Aside from the successful anti-VEGF therapies, antibodies targeting the complement pathway show some promise. Because activation of the alternative complement pathway contributes to AMD pathology, antibodies targeting components of this pathway, such as C3 and C5, may attenuate inflammation and damage to the retina by reducing complement mediated cell lysis [53,54].…”

Section: Potential Therapeutics For Amdmentioning

confidence: 99%

“…Gene therapy involves introducing genetic material, typically a viral vector, into tissues of interest to replace the blueprint of a protein product. The most used viral vectors are adeno-associated viral vectors due to their lower immunogenicity and extended duration of gene expression [54].…”

Section: Potential Therapeutics For Amdmentioning

confidence: 99%

“…In contrast, the RPE does not have neural connections, but serves to maintain healthy photoreceptors by providing nutrients and removing waste products. For these reasons, the RPE is currently the primary target of cell-based therapy for AMD [54]. Another promising cellular therapy for exudative AMD is replacement of the choroidal endothelial layer as this may prevent neovascularization [55].…”

Section: Potential Therapeutics For Amdmentioning

confidence: 99%

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An Overview of Age-Related Macular Degeneration: Clinical, Pre-Clinical Animal Models and Bidirectional Translation

Rho¹,

Percelay²,

Pilkinton³

et al. 2022

Preclinical Animal Modeling in Medicine

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Age-related macular degeneration (AMD) is a multifactorial disease that results from a complex and unknown interplay among environmental, genetic, and epidemiologic factors. Risk factors include aging, family history, obesity, hypercholesterolemia, and hypertension, along with cigarette smoking, which is the most influential modifiable risk factor. Single nucleotide polymorphisms (SNPs) in numerous genes such as complement factor H (CFH) pose some of the known genetic risks. The pathophysiology in AMD is incompletely understood, but is known to involve oxidative stress, inflammation, dysregulated antioxidants, lipid metabolism, and angiogenesis. Animal models have been integral in expanding our knowledge of AMD pathology. AMD is classified as non-exudative or exudative. Because there is no perfect animal model that recapitulates all aspects of the human disease, rodents, rabbits, and non-human primates offer different advantages and disadvantages to serve as models for various aspects of the disease. Scientific advances have also allowed for the creation of polygenic pre-clinical models that may better represent the complexity of AMD, which will likely expand our knowledge of disease mechanisms and serve as platforms for testing new therapeutics. There have been, and there continues to be, many drugs in the pipeline to treat both exudative and non-exudative AMD. However, Food and Drug Administration (FDA)-approved therapies for exudative AMD that mainly target angiogenic growth factors are the only therapeutics currently being used in the clinics. There remains no FDA-approved therapy for the non-exudative form of this disease. This chapter contains a basic overview and classification of AMD and multiple animal models of AMD are highlighted. We include an overview of both current FDA-approved treatments and those in development. Lastly, we conclude with a summary of the important role of pre-clinical studies in the development of therapeutics for this highly prevalent disease.

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<p>Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration</p>

Cited by 19 publications

References 58 publications

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

An Overview of Age-Related Macular Degeneration: Clinical, Pre-Clinical Animal Models and Bidirectional Translation

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