Abstract:
:Recombinant adeno-associated virus (AAV) is the leading vector for gene therapy in the retina. As non-pathogenic, non-integrating, replication deficient vector, the recombinant virus efficiently transduces all key retinal cell populations. Successful testing of AAV vectors in clinical trials of inherited retinal diseases led to the recent approval of voretigene neparvovec (Luxturna) for the treatment of RPE65 mutation-associated retinal dystrophies. However, studies applying AAV-mediated retinal gene therapy independently reported intraocular inflammation and/or loss of efficacy after initial functional improvements. Both observations might be explained by targeted removal of transduced cells via anti-viral defence mechanisms. AAV has been shown to activate innate pattern recognition receptors (PRRs) such as toll-like receptor (TLR)-2 and TLR-9 resulting in the release of inflammatory cytokines and type I interferons. The vector can also induce capsid-specific and transgene-specific T cell responses and neutralizing anti-AAV antibodies which both limit the therapeutic effect. However, the target organ of retinal gene therapy, the eye, is known as an immune-privileged site. It is characterized by suppression of inflammation and promotion of immune tolerance which might prevent AAV-induced immune responses. This review evaluates AAV-related immune responses, toxicity and inflammation in studies of retinal gene therapy, identifies influencing variables of these responses and discusses potential strategies to modulate immune reactions to AAV vectors to increase the safety and efficacy of ocular gene therapy.
journal_name
Prog Retin Eye Resjournal_title
Progress in retinal and eye researchauthors
Bucher K,Rodríguez-Bocanegra E,Dauletbekov D,Fischer MDdoi
10.1016/j.preteyeres.2020.100915subject
Has Abstractpub_date
2020-10-15 00:00:00pages
100915eissn
1350-9462issn
1873-1635pii
S1350-9462(20)30087-2pub_type
杂志文章,评审abstract::Axonal degeneration is an active, highly controlled process that contributes to beneficial processes, such as developmental pruning, but also to neurodegeneration. In glaucoma, ocular hypertension leads to vision loss by killing the output neurons of the retina, the retinal ganglion cells (RGCs). Multiple processes ha...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2019.07.002
更新日期:2019-11-01 00:00:00
abstract::Understanding of corneal wound healing plays an important role, not only in management of corneal infections, but especially in refractive surgery. A better control of wound healing mechanisms might improve the results of such resculpturing techniques and help to avoid complications arising from these procedures. Whil...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/s1350-9462(02)00064-2
更新日期:2003-05-01 00:00:00
abstract::The patterns of eye movement that accompany static activities such as reading have been studied since the early 1900s, but it is only since head-mounted eye trackers became available in the 1980s that it has been possible to study active tasks such as walking, driving, playing ball games and ordinary everyday activiti...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2006.01.002
更新日期:2006-05-01 00:00:00
abstract::Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including anti...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2013.12.004
更新日期:2014-05-01 00:00:00
abstract::The dedicator of cytokinesis (Dock) family is composed of atypical guanine exchange factors (GEFs) that activate the Rho GTPases Rac1 and Cdc42. Rho GTPases are best documented for their roles in actin polymerization and they regulate important cellular functions, including morphogenesis, migration, neuronal developme...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2014.06.005
更新日期:2014-11-01 00:00:00
abstract::Regeneration of visual pigments is essential for sustained visual function. Although the requirement for non-photochemical regeneration of the visual chromophore, 11-cis-retinal, was recognized early on, it was only recently that the trans to cis retinoid isomerase activity required for this process was assigned to a ...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2010.03.002
更新日期:2010-09-01 00:00:00
abstract::Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, interact in the juxtacanalicular tissue (JCT) region of the conve...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2014.08.002
更新日期:2015-01-01 00:00:00
abstract::The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier by regulating the movement of solutes between the fenestrated capillaries of the choroid and the photoreceptor layer of the retina. Blood-tissue barriers use various mechanisms to accomplish their tasks including membrane pumps, transporters, a...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2011.06.002
更新日期:2011-09-01 00:00:00
abstract::Vision is the most important sense for humans and it is irreversibly impaired by axonal damage of retinal ganglion cells (RGCs) in the optic nerve due to the lack of axonal regeneration. The failure of regeneration is partially attributable to factors located in the inhibitory environment of the forming glial scar and...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2012.06.005
更新日期:2012-11-01 00:00:00
abstract::The eye is an ideal target for exploiting the potential of human induced pluripotent stem cell (hiPSC) technology in order to understand disease pathways and explore novel therapeutic strategies for inherited retinal disease. The aim of this article is to map the pathway from state-of-the art laboratory-based discover...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2013.09.002
更新日期:2013-11-01 00:00:00
abstract::Catalyzed by endothelial nitric oxide (NO) synthase (eNOS) activity, NO is a gaseous signaling molecule maintaining endothelial and cardiovascular homeostasis. Principally, NO regulates the contractility of vascular smooth muscle cells and permeability of endothelial cells in response to either biochemical or biomecha...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2020.100922
更新日期:2020-11-28 00:00:00
abstract::The macular pigments (MP) absorb light in the blue-green region of the visible spectrum and comprise two carotenoids, lutein and zeaxanthin. In humans the concentration of MP varies widely across the normal population. There are two (not mutually exclusive) proposed roles for MP: to improve visual function and to act ...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2004.05.004
更新日期:2004-09-01 00:00:00
abstract::The rationale behind hyperacute fibrinolytic therapy for cerebral and retinal arterial occlusion is to rescue ischaemic cells from irreversible damage through timely restitution of tissue perfusion. In cerebral stroke, an anoxic tissue compartment (the "infarct core") is surrounded by a hypoxic compartment (the "ischa...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2015.06.001
更新日期:2015-11-01 00:00:00
abstract::Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular dege...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2012.03.004
更新日期:2012-07-01 00:00:00
abstract::The vitreous gel is a transparent extracellular matrix that fills the cavity behind the lens of the eye and is surrounded by and attached to the retina. This gel liquefies during ageing and in 25-30% of the oppulation the residual gel structure eventually collapses away from the posterior retina in a process called po...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/s1350-9462(99)00016-6
更新日期:2000-05-01 00:00:00
abstract::Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because of eye pathology studies showing high cholesterol content of drusen, aging Bruch's membr...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2014.03.002
更新日期:2014-07-01 00:00:00
abstract::Cells of the human retinal pigment epithelium (RPE) have a regular epithelial cell shape within the tissue in situ, but for reasons that remain elusive the RPE shows an incomplete and variable ability to re-develop an epithelial phenotype after propagation in vitro. In other epithelial cell cultures, formation of an a...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2008.08.002
更新日期:2008-11-01 00:00:00
abstract::Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, ...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2008.02.002
更新日期:2008-05-01 00:00:00
abstract::Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2011.09.001
更新日期:2012-01-01 00:00:00
abstract::Gene expression provides valuable insight into cell function. As such, vision researchers have frequently employed gene expression studies to better understand retinal physiology and disease. With the advent of single-cell RNA sequencing, expression experiments provide an unparalleled resolution of information. Instea...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2020.100934
更新日期:2020-12-28 00:00:00
abstract::Phototransduction in vertebrate photoreceptor cells mediated by rhodopsin is one of the most comprehensively examined G protein-coupled receptor (GPCR) signaling pathways. The signal transduction pathway can be mapped from the initial absorption of light to conformational changes within rhodopsin, through activation o...
journal_title:Progress in retinal and eye research
pub_type: 历史文章,杂志文章,评审
doi:10.1016/s1350-9462(03)00017-x
更新日期:2003-07-01 00:00:00
abstract::The refractive power of a lens is determined largely by its surface curvatures and the refractive index of its medium. These properties can also be used to control the sharpness of focus and hence the image quality. One of the most effective ways of doing this is with a gradient index. Eye lenses of all species, thus ...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章
doi:10.1016/j.preteyeres.2012.03.001
更新日期:2012-07-01 00:00:00
abstract::Autophagy is a catabolic pathway that promotes the degradation and recycling of cellular components. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. In response to stress, autophagy mediates the degradation of cell components, which are recycled...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2016.08.001
更新日期:2016-11-01 00:00:00
abstract::Glaucoma is a common neurodegenerative disease that affects retinal ganglion cells (RGCs). Substantial effort is being expended to determine how RGCs die in glaucoma. As in other neurodegenerative diseases, the majority of effort focuses on characterising apoptotic self-destruct pathways. However, apoptosis is not the...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2005.04.004
更新日期:2005-11-01 00:00:00
abstract::Light-emitting diodes (LEDs) are taking an increasing place in the market of domestic lighting because they produce light with low energy consumption. In the EU, by 2016, no traditional incandescent light sources will be available and LEDs may become the major domestic light sources. Due to specific spectral and energ...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2011.04.002
更新日期:2011-07-01 00:00:00
abstract::Age-related diseases, including age-related macular degeneration (AMD), are of growing importance in a world where population ageing has become a dominant global trend. Although a wide variety of risk factors for AMD have been identified, age itself remains by far the most important risk factor, making it an urgent pr...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2019.100825
更新日期:2020-05-01 00:00:00
abstract::The retinal pigment epithelium (RPE) maintains retinal function as the metabolic gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to induce age-related macular degeneration (AMD) in susceptible individuals. Unl...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2007.02.002
更新日期:2007-09-01 00:00:00
abstract::The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connec...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2012.02.003
更新日期:2012-05-01 00:00:00
abstract::Morphometrics, a branch of morphology, represents the study of size and shape components of biological form and their variation in the population. Assessment of optic disc morphology is essential in the diagnosis and management of many ophthalmic disorders. Much work has been performed to characterize size-related par...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/j.preteyeres.2009.05.004
更新日期:2009-07-01 00:00:00
abstract::Uveitis is a major cause of blindness, with the visual loss that occurs being due primarily to retinal tissue damage. The tissue damage is mediated mainly by phagocytic inflammatory cells, such as macrophages, by the release of various proteolytic enzymes, arachidonic acid metabolites, cytokines and free radicals. The...
journal_title:Progress in retinal and eye research
pub_type: 杂志文章,评审
doi:10.1016/s1350-9462(99)00003-8
更新日期:2000-01-01 00:00:00