scholarly journals Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium

10.3791/53030 ◽  
2015 ◽  
Author(s):  
Sung Wook Park ◽  
Jin Hyoung Kim ◽  
Woo Jin Park ◽  
Jeong Hun Kim
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Viral Vectors ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subretinal Injection

scholarly journals Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease

2017 ◽  
Vol 114 (15) ◽  
pp. 3987-3992 ◽  
Author(s):  
Tamara L. Lenis ◽  
Shanta Sarfare ◽  
Zhichun Jiang ◽  
Marcia B. Lloyd ◽  
Dean Bok ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Complement System ◽  
Complement Activation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Host Cells ◽  
Etiologic Factor ◽  
Photoreceptor Degeneration ◽  
The Complement System

Recessive Stargardt macular degeneration (STGD1) is caused by mutations in the gene for the ABCA4 transporter in photoreceptor outer segments. STGD1 patients and Abca4−/− (STGD1) mice exhibit buildup of bisretinoid-containing lipofuscin pigments in the retinal pigment epithelium (RPE), increased oxidative stress, augmented complement activation and slow degeneration of photoreceptors. A reduction in complement negative regulatory proteins (CRPs), possibly owing to bisretinoid accumulation, may be responsible for the increased complement activation seen on the RPE of STGD1 mice. CRPs prevent attack on host cells by the complement system, and complement receptor 1-like protein y (CRRY) is an important CRP in mice. Here we attempted to rescue the phenotype in STGD1 mice by increasing expression of CRRY in the RPE using a gene therapy approach. We injected recombinant adeno-associated virus containing the CRRY coding sequence (AAV-CRRY) into the subretinal space of 4-wk-old Abca4−/− mice. This resulted in sustained, several-fold increased expression of CRRY in the RPE, which significantly reduced the complement factors C3/C3b in the RPE. Unexpectedly, AAV-CRRY–treated STGD1 mice also showed reduced accumulation of bisretinoids compared with sham-injected STGD1 control mice. Furthermore, we observed slower photoreceptor degeneration and increased visual chromophore in 1-y-old AAV-CRRY–treated STGD1 mice. Rescue of the STGD1 phenotype by AAV-CRRY gene therapy suggests that complement attack on the RPE is an important etiologic factor in STGD1. Modulation of the complement system by locally increasing CRP expression using targeted gene therapy represents a potential treatment strategy for STGD1 and other retinopathies associated with complement dysregulation.

scholarly journals Intercellular Trafficking of Adenovirus-Delivered HSV VP22 from the Retinal Pigment Epithelium to the Photoreceptors—Implications for Gene Therapy

2002 ◽  
Vol 6 (6) ◽  
pp. 813-823 ◽  
Author(s):  
Siobhan M. Cashman ◽  
Sonia L. Sadowski ◽  
David J. Morris ◽  
Jeanne Frederick ◽  
Rajendra Kumar-Singh
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Intercellular Trafficking

scholarly journals 522. Neural Retina Limits Delivery Non Viral Vectors to Retinal Pigment Epithelium

2006 ◽  
Vol 13 ◽  
pp. S200-S201
Author(s):  
Liesbeth Peeters ◽  
Niek Sanders ◽  
Koen Boussery ◽  
Johan Van de Voorde ◽  
Joseph Demeester ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Viral Vectors ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neural Retina

Choroideremia

2021 ◽  
pp. 213-217
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Visual Acuity ◽  
Retinal Pigment Epithelium ◽  
Small Molecules ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Prosthesis ◽  
Progressive Reduction ◽  
Progressive Degeneration

Choroideremia is X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE), and retina. The disease is caused by mutations in the CHM gene which is known to be related to membrane transportation protein in the retina and RPE. Male-affected cases have nyctalopia and progressive reduction in visual acuity. Female-affected cases are carriers. This disease is considered incurable, although new promising treatments have been recently introduced such as gene therapy, stem cells, small molecules, and retinal prosthesis.

scholarly journals Advantages of robotic assistance over a manual approach in simulated subretinal injections and its relevance for gene therapy

Gene Therapy ◽  
2021 ◽  
Author(s):  
Reza Ladha ◽  
Thijs Meenink ◽  
Jorrit Smit ◽  
Marc D. de Smet
Keyword(s):  
Gene Therapy ◽  
Clinical Success ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Genetic Diseases ◽  
Cost Effective ◽  
Robotic Assistance ◽  
Injection Duration ◽  
Retinal Hole ◽  
Subretinal Injection

AbstractSubretinal injection is a method for gene delivery to treat genetic diseases of the photoreceptors and retinal pigment epithelium. A reflux-free subretinal injection is important to allow effective, safe, and cost-effective gene therapy to the retina. We report on a comparison between manual and robotic assistance in simulated subretinal injections using an artificial retina model. Nine surgeons carried out the procedure with and without the Preceyes Surgical System, using an OPMI Lumera 700 Zeiss surgical microscope equipped with intra-operative optical coherence tomography. Success in creating a bleb without reflux, injection duration, drift, tremor, and increase in the diameter of the puncture hole were analyzed. Robotic assistance improved drift (median 16 vs 212 µm), tremor (median 1 vs 18 µm), enlargement of the retinal hole, and allowed for prolonged injection times (median 52 vs 29 sec). Robotic assistance allowed higher rate of bleb formation (8/9 vs 4/9 attempts) with a moderate reduction in reflux (7/9 vs 8/9 attempts) in this artificial model. Robotic assistance can significantly contribute to subretinal injections and provide quantifiable parameters in assessing surgical and clinical success of novel retinal gene therapies.

scholarly journals Adeno-Associated Viral Vectors as a Tool for Large Gene Delivery to the Retina

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 287 ◽  
Author(s):  
Trapani
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Considerable Effort ◽  
Safety And Efficacy ◽  
Large Gene ◽  
Packaging Capacity ◽  
Large Genes

Gene therapy using adeno-associated viral (AAV) vectors currently represents the most promising approach for the treatment of many inherited retinal diseases (IRDs), given AAV’s ability to efficiently deliver therapeutic genes to both photoreceptors and retinal pigment epithelium, and their excellent safety and efficacy profiles in humans. However, one of the main obstacles to widespread AAV application is their limited packaging capacity, which precludes their use from the treatment of IRDs which are caused by mutations in genes whose coding sequence exceeds 5 kb. Therefore, in recent years, considerable effort has been made to identify strategies to increase the transfer capacity of AAV vectors. This review will discuss these new developed strategies, highlighting the advancements as well as the limitations that the field has still to overcome to finally expand the applicability of AAV vectors to IRDs due to mutations in large genes.

scholarly journals Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient

2014 ◽  
Vol 1 ◽  
pp. 14011 ◽  
Author(s):  
Nicolas Cereso ◽  
Marie O Pequignot ◽  
Lorenne Robert ◽  
Fabienne Becker ◽  
Valerie De Luca ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Proof Of Concept

scholarly journals A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium

Biomaterials ◽  
2013 ◽  
Vol 34 (29) ◽  
pp. 7158-7167 ◽  
Author(s):  
Adarsha Koirala ◽  
Shannon M. Conley ◽  
Muna I. Naash
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Viral Gene ◽  
Viral Gene Therapy
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