The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases

Desideri, Lorenzo Ferro; Traverso, Carlo Enrico; Nicolò, Massimo

doi:10.1080/14728222.2022.2036121

Cited by 27 publications

(21 citation statements)

References 74 publications

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“…Intravitreal faricimab has hypothetical advantages over aflibercept, including a greater affinity for VEGFA as well as neutralizing Ang2, which research has implicated in the pathophysiology of angiogenesis. [12][13][14] However, as mentioned in the Introduction, the pivotal trials YOSEMITE and RHINE did not allow subjects randomized to aflibercept to receive a personalized treatment plan, regardless of the subject's clinical course. 4 The authors would have favored an identical treatment protocol among subjects receiving IVA and IVF in order to better evaluate comparative effectiveness between treatments.…”

Section: Resultsmentioning

confidence: 99%

Faricimab for Treatment-Resistant Diabetic Macular Edema

Rush¹,

Rush²

2022

OPTH

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To assess the short-term outcomes in treatment-resistant diabetic macular edema (DME) patients changed from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF). Methods: A retrospective review was undertaken on DME subjects receiving IVA therapy at a single private practice. Patients were separated into study and control cohorts. Both study and control patients had received more than or equal to six IVA injections during the preceding 12 months, more than or equal to four IVA injections during the preceding 6 months, had a central macular thickness (CMT) on optical coherence tomography (OCT) of ≥300 µm, and had retinal fluid on OCT before cohort assignment. Study patients were switched to IVF and underwent three injections within 4 months, whereas control patients stayed on IVA during the same period and received three injections within 4 months. Results: There were 51 patients analyzed. There were 37.5% (9/24) in the study group and 3.7% (1/27) in the control group who achieved a CMT of less than 300 µm without retinal fluid on OCT at the end of the 4-month study (p=0.001). There were 41.7% (10/24) in the study group and 11.1% (3/27) in the control group who had gained two or more lines of visual acuity at the end of the 4-month study (p=0.01). Conclusion: For a significant minority, IVF can improve the short-term visual and anatomic outcomes in treatment-resistant DME patients formerly managed with IVA. Longer follow-up is needed to determine if such improvements can be preserved.

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Section: Resultsmentioning

confidence: 99%

Faricimab for Treatment-Resistant Diabetic Macular Edema

Rush¹,

Rush²

2022

OPTH

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“…Reservoirs were designed to maintain large, fluidic volumes for multi-day testing, and the electrode assembly can apply a range of electrical fields to stimulate SC motility ( Figure 5 ). This design facilitates the application of electric fields currently used in animal studies and in the clinic, such as treatments with biochemical agents [ 76 , 77 ] and low level electric fields [ 78 , 79 ]. Electrical activity is known to play an important role in the formation and connectivity of neural circuits, where EF can modify synaptic connectivity, the structure of neuronal projections, and induce changes in gene expression, protein synthesis, and intrinsic excitability (reviewed in [ 80 , 81 ]).…”

Section: Discussionmentioning

confidence: 99%

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

2022

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Millions of adults are affected by progressive vision loss worldwide. The rising incidence of retinal diseases can be attributed to damage or degeneration of neurons that convert light into electrical signals for vision. Contemporary cell replacement therapies have transplanted stem and progenitor-like cells (SCs) into adult retinal tissue to replace damaged neurons and restore the visual neural network. However, the inability of SCs to migrate to targeted areas remains a fundamental challenge. Current bioengineering projects aim to integrate microfluidic technologies with organotypic cultures to examine SC behaviors within biomimetic environments. The application of neural phantoms, or eye facsimiles, in such systems will greatly aid the study of SC migratory behaviors in 3D. This project developed a bioengineering system, called the μ-Eye, to stimulate and examine the migration of retinal SCs within eye facsimiles using external chemical and electrical stimuli. Results illustrate that the imposed fields stimulated large, directional SC migration into eye facsimiles, and that electro-chemotactic stimuli produced significantly larger increases in cell migration than the individual stimuli combined. These findings highlight the significance of microfluidic systems in the development of approaches that apply external fields for neural repair and promote migration-targeted strategies for retinal cell replacement therapy.

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“…The frequency of vision improvement in the ranibizumab group was twice that of the laser group. Notably, in contrast to the eyes mainly exposed to laser treatment alone, the eyes exposed to laser and ranibizumab treatment are less probably to show significant vision loss ( 268 ). Diabetic individuals suffer more risk of cataracts that require surgical treatment.…”

Section: Treatment Of Diabetic Nephropathy and Diabetic Retinopathymentioning

confidence: 99%

“…The concentration of VEGF in the eye is closely related to hypoxia and active neovascularization. After laser photocoagulation, its concentration decreases, and VEGF inhibitor active drugs can improve ischemia-induced animal retinal neovascularization and prevent or even realize the reversal of PDR and DME ( 268 , 269 ). A random trial contrasted laser treatment + intravitreous ranibizumab injection with laser treatment + placebo injection in DME sufferers ( 268 ).…”

Section: Treatment Of Diabetic Nephropathy and Diabetic Retinopathymentioning

confidence: 99%

“…After laser photocoagulation, its concentration decreases, and VEGF inhibitor active drugs can improve ischemia-induced animal retinal neovascularization and prevent or even realize the reversal of PDR and DME ( 268 , 269 ). A random trial contrasted laser treatment + intravitreous ranibizumab injection with laser treatment + placebo injection in DME sufferers ( 268 ). In the first year, the ranibizumab group gained approximately single-line extra vision compared to laser treatment.…”

Section: Treatment Of Diabetic Nephropathy and Diabetic Retinopathymentioning

confidence: 99%

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Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

Yang

Liu

2022

Front. Endocrinol.

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Diabetic nephropathy (DN) and diabetic retinopathy (DR) are microvascular complications of diabetes. Microvascular endothelial cells are thought to be the major targets of hyperglycemic injury. In diabetic microvasculature, the intracellular hyperglycemia causes damages to the vascular endothelium, via multiple pathophysiological process consist of inflammation, endothelial cell crosstalk with podocytes/pericytes and exosomes. In addition, DN and DR diseases development are involved in several critical regulators including the cell adhesion molecules (CAMs), the vascular endothelial growth factor (VEGF) family and the Notch signal. The present review attempts to gain a deeper understanding of the pathogenesis complexities underlying the endothelial dysfunction in diabetes diabetic and retinopathy, contributing to the development of new mechanistic therapeutic strategies against diabetes-induced microvascular endothelial dysfunction.

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The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases

Cited by 27 publications

References 74 publications

Faricimab for Treatment-Resistant Diabetic Macular Edema

Faricimab for Treatment-Resistant Diabetic Macular Edema

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

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