Gene Therapy for Retinal Disease

McClements, Michelle E.; MacLaren, Robert E.

doi:10.1016/b978-0-12-800563-7.00011-7

Cited by 3 publications

(4 citation statements)

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“…In different vari-eties of chronic granulomatous disease some cells of the immune system can engulf certain pathogenic bacteria and fungi but cannot generate the chemicals needed to kill them, thus reducing the body's ability to fight infections. Other clinical trials have reported some success with treating Leber congenital amaurosis, a cause of blindness, and beta-thalassemia, which involves problems with producing hemoglobin [17,20,22].…”

Section: Potential Applications Of Gene Therapy and Genetic Modificationmentioning

confidence: 97%

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Genetic Engineering: Tinkering with the Human Body

Stratmann¹

2015

Science and Fiction

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Section: Potential Applications Of Gene Therapy and Genetic Modificationmentioning

confidence: 97%

“…Over 200 genes can show mutations that produce inherited retinal diseases [22,77,78]. Development of the most common form of this problem, retinitis pigmentosa, has been associated with at least 30 genes itself.…”

Section: Repairing and Enhancing The Human Bodymentioning

confidence: 99%

Genetic Engineering: Tinkering with the Human Body

Stratmann¹

2015

Science and Fiction

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“…While invasive, the microinjection of virus into humans has been used in the retina and in the brain for treatment of Parkinson disease and Alzheimer disease and appears safe and effective to express proteins. 13,14 However, assuring dosage, safety and reversibility of the viral approach will be important to its success in humans. Potentially newer technologies, such as TAT-mediated protein transduction or liposome-mediated plasmid transfection, may evolve for non viral delivery of channelrhodopsin to neurons.…”

Section: Viral Targetingmentioning

confidence: 99%

Light up your life: Optogenetics for depression?

Albert

2014

J Psychiatry Neurosci

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In the last year, several new studies have shown the potential of optogenetic stimulation to rapidly modify depression-and anxiety-related behaviours in animal models. Optogenetic technology, as described in a previous editorial, 1 gives a whole new meaning to "light therapy" that is potentially more effective and rapid and has fewer adverse effects than classic light therapy or pharmacological approaches to treat mental illness.Unlike classic light therapy, which involves a generalized effect of photic stimulation of the visual system to medi ate its effects, 2 optogenetics involves the activation by light of engineered light-sensitive ion channel proteins expressed in cells of interest.3 These light-sensitive channels respond to different colors: channelrhodopsin is activated by blue light and depolarizes to activate neurons, while halorhodopsin is activated by yellow light and hyperpolarizes, inhibiting neuronal activity. Viruses have been generated that can express the light-sensitive channel directly or that express the Cre recombinase to trigger its expression in transgenic animals. For in vivo studies the virus is injected into the brain region of interest, and the channel is activated by light fibres implanted at the region of interest in live behaving animals. Recent studies using optogenetic approaches in mice suggest that stimulation by either laseror LED light at wavelengths to activate channelrhodopsin expressed in transgenically targeted dopamine neurons in the ventral tegmental area (VTA) can mediate an immediate effect in 2 models of depression. 4,5 Importantly, the pattern of stimulation was critical, with phasic but not tonic light stimulation mediating the effect. Interestingly, in the social defeat model phasic stimulation resulted in increased susceptibility to depression-like behaviour, while inhibition of the same neurons conferred resilience.4 By contrast, in a chronic mild stress model of depression, phas ic stimulation conferred resistance and inhibition induced depression-like behaviour in forced swim, tail suspension and sucrose preference tests.5 Why these results of stimulating or inhibiting VTA dopamine neurons are opposite is unclear, but it could relate to differences between the models: social defeat is an acute high-stress treatment that induces social isolation and anhedonia-like behaviour and may model posttraumatic stress disorder. 6 Chronic mild stress subjects mice to a repeated low level of inescapable stress that is more akin to depression in humans. Phasic activation of the VTA, while considered a reward pathway, is more accurately a salience monitor for both positive and negative events.7 Its activation is induced by social defeat, and optogenetic activation triggers the negative salience behavioural response. 4 While in chronic mild stress, phasic VTA activation may trigger motivated behaviour, counteracting the demotivating effects of this paradigm.Several studies have shown the importance of region-and cell-specific activation of channelrhodopsin in triggering anxie...

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“…Retinal degenerative disorders are the leading cause of irreversible blindness worldwide (McClements and MacLaren 2013). Some wellstudied diseases within this large and heterogenous group are age-related macular degeneration (AMD), retinitis pigmentosa, Stargardt disease, Leber congenital amaurosis, and Best disease, to name just a few.…”

mentioning

confidence: 99%