A Brief Account of Rho GTPases in Retinal Physiology and Pathophysiology

Heynen, Severin R.; Ogunshola, Omolara O.; Grimm, Christian

doi:10.1007/978-1-4614-0631-0_74

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…12 As a Rho GTPase implicated in retinal degenerative diseases. 13 RhoB also supports the expression of multiple VEGF receptors in endothelial cells (VEGFR1, VEGFR2, and NRP1), acting at the level of transcription by direct interaction with the proangiogenic transcription factor DB1/VEZF1. 5 Thus, RhoB acts at several levels to modify VEGF signaling in the setting of pathogenic angiogenesis.…”

Section: Introductionmentioning

confidence: 92%

“…RhoB modifies Akt trafficking in endothelial cells where Akt serves as a key mediator of VEGF receptor signaling . As a Rho GTPase implicated in retinal degenerative diseases . RhoB also supports the expression of multiple VEGF receptors in endothelial cells (VEGFR1, VEGFR2, and NRP1), acting at the level of transcription by direct interaction with the proangiogenic transcription factor DB1/VEZF1 .…”

Section: Introductionmentioning

confidence: 99%

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RhoB antibody alters retinal vascularization in models of murine retinopathy

Almonte-Baldonado

Bravo‐Nuevo

Gerald

et al. 2018

J of Cellular Biochemistry

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Neovascularization in cancer or retinopathy is driven by pathological changes that foster abnormal sprouting of endothelial cells. Mouse genetic studies indicate that the stress-induced small GTPase RhoB is dispensable for normal physiology but required for pathogenic angiogenesis. In diabetic retinopathy, retinopathy of prematurity (ROP) or age-related wet macular degeneration (AMD), progressive pathologic anatomic changes and ischemia foster neovascularization are characterized by abnormal sprouting of endothelial cells. This process is driven by the angiogenic growth factor VEGF, which induces and supports the formation of new blood vessels. While injectable biologics targeting VEGF have been used to treat these pathological conditions, many patients respond poorly, prompting interest in other types of mechanism-based therapy.Here we report the preclinical efficacy of a monoclonal antibody that specifically targets RhoB, a signaling molecule that is genetically dispensable for normal physiology but required for pathogenic retinal angiogenesis. In murine models of proliferative retinal angiogenesis or oxygen-induced retinopathy, administering a monoclonal RhoB antibody (7F7) was sufficient to block neoangiogenesis or avascular pathology, respectively. Our findings offer preclinical proof of concept for antibody targeting of RhoB to limit diabetic retinopathy, ROP or wet AMD and perhaps other diseases of neovasculogenesis such as hemangioma or hemangiosarcoma nonresponsive to existing therapies. K E Y W O R D S animal model, diabetic retinopathy, macular degeneration, monoclonal antibody, oxygen-induced retinopathy (OIR), retinopathy of prematurity (ROP), Rho GTPase

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

RhoB antibody alters retinal vascularization in models of murine retinopathy

Almonte-Baldonado

Bravo‐Nuevo

Gerald

et al. 2018

J of Cellular Biochemistry

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“…Evidence for their importance in sensory neuron development, differentiation and survival is diverse and scattered through all sensory systems, such as cochlear hair cells [70,71], retinal photoreceptors [72] and somatosensory primary afferents including nociceptors [8,73,74]. Novel optogenetic and chemogenetic tools are increasingly available to experimentally target Rho GTPases and are extensively used in retinal and cochlear sensory neurons [75].…”

Section: Rho Gtpases In Developing and Mature Sensory Neuronsmentioning

confidence: 99%

Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons

Kalpachidou

Spiecker

Kress

et al. 2019

Cells

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Numerous experimental studies demonstrate that the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases) Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42) are important regulators in somatosensory neurons, where they elicit changes in the cellular cytoskeleton and are involved in diverse biological processes during development, differentiation, survival and regeneration. This review summarizes the status of research regarding the expression and the role of the Rho GTPases in peripheral sensory neurons and how these small proteins are involved in development and outgrowth of sensory neurons, as well as in neuronal regeneration after injury, inflammation and pain perception. In sensory neurons, Rho GTPases are activated by various extracellular signals through membrane receptors and elicit their action through a wide range of downstream effectors, such as Rho-associated protein kinase (ROCK), phosphoinositide 3-kinase (PI3K) or mixed-lineage kinase (MLK). While RhoA is implicated in the assembly of stress fibres and focal adhesions and inhibits neuronal outgrowth through growth cone collapse, Rac1 and Cdc42 promote neuronal development, differentiation and neuroregeneration. The functions of Rho GTPases are critically important in the peripheral somatosensory system; however, their signalling interconnections and partially antagonistic actions are not yet fully understood.

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A Brief Account of Rho GTPases in Retinal Physiology and Pathophysiology

Cited by 2 publications

References 37 publications

RhoB antibody alters retinal vascularization in models of murine retinopathy

RhoB antibody alters retinal vascularization in models of murine retinopathy

Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons

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