Surgical Approaches to Gene and Stem Cell Therapy for Retinal Disease

Stout, J. Timothy; Francis, Peter J.

doi:10.1089/hum.2011.060

Cited by 30 publications

(26 citation statements)

References 33 publications

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“…A number of subretinal injection procedures, particularly in the macular area, have made use of a transvitreal approach following a pars plana vitrectomy. [27][28][29] While many have used small-gauge nonextendible cannulas, some (including Komaromy and colleagues 30 ) have proposed an extendable microneedle for improved subretinal injection. Nevertheless, subretinal delivery through a transvitreal approach remains challenging.…”

Section: Discussionmentioning

confidence: 99%

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Smet¹,

Lynch

Dejneka

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study evaluated a new subretinal method for delivery of human or pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel subretinal injection cannula and suprachoroidal approach in Göttingen minipig eyes. hUTC (palucorcel) are currently under development for treating geographic atrophy in humans.METHODS. Twenty-four Göttingen minipigs (divided into eight groups) were subretinally administered palucorcel, pUTC, or vehicle. In some cases, fluorescently labeled cells and vehicle were administered. Conjunctival cutdown and sclerotomy were performed, then a flexible cannula containing a microneedle was inserted and advanced into the suprachoroidal space. The microneedle was deployed and visualized; 50 lL cells (target concentration, 11.2 3 10 6 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety outcomes were evaluated.RESULTS. For all animals, cells and vehicle were successfully administered. Labeled cells or fluorescent vehicle were contained in the subretinal bleb, without leakage into the vitreous. No retinal detachment or vitreous traction band was identified by ophthalmologic examination. At all time points, observed microscopic changes were attributable to experimental procedures. On histopathology immediately after injection, localized retinal detachments were seen, along with focal retinal, choroidal, and/or scleral discontinuities. A moderate inflammatory response was seen in a limited number of animals. In the allogeneic setting, no antibody responses were detectable. Anti-human UTC antibodies were detected in the xenogeneic setting.CONCLUSIONS. Palucorcel, pUTC, and vehicle were successfully administered to Göttingen minipigs using a novel subretinal injection cannula via a suprachoroidal surgical approach, with no significant adverse events; therefore, this technique appears to be feasible for further clinical development.

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Section: Discussionmentioning

confidence: 99%

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Smet¹,

Lynch

Dejneka

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…However, regarding this delivery route, short-term complications including retinal detachment, endophthalmitis, and hemorrhage have to be noted [88,91] . Moreover, intravitreal injection has a weak effect on some other drugs targeting the cells in subretinal spaces (RPE cells, for instance) because of the barriers (e.g., the internal limiting membrane) between the retina and RPE cells [92,93] . It might also represent the injection of an unnecessarily high dose of the drug into the vitreous.…”

Section: Subretinal Delivery Versus Intravitreal Injection?mentioning

confidence: 99%

“…It might also represent the injection of an unnecessarily high dose of the drug into the vitreous. Compared to intravitreal injection, subretinal delivery of viral vectors is thought to be the most efficient transduction of neurosensory retina and RPE [92] . It provides a direct route with more precise localization via a minimally invasive injection.…”

Section: Subretinal Delivery Versus Intravitreal Injection?mentioning

confidence: 99%

Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases

Peng

Tang

Zhou³

2017

Ophthalmic Res

133

117

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Compared to intravitreal injection, subretinal injection has more direct effects on the targeting cells in the subretinal space, which provides a new therapeutic method for vitreoretinal diseases, especially when gene therapy and/or cell therapy is involved. To date, subretinal delivery has been widely applied by scientists and clinicians as a more precise and efficient route of ocular drug delivery for gene therapies and cell therapies including stem cells in many degenerative vitreoretinal diseases, such as retinitis pigmentosa, age-related macular degeneration, and Leber's congenital amaurosis. However, clinicians should be aware of adverse events and possible complications when performing subretinal delivery. In the present review, the subretinal injection used in vitreoretinal diseases for basic research and clinical trials is summarized and described. Different methods of subretinal delivery, as well as its benefits and challenges, are also briefly introduced.

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“…2007; Caramoy et al. 2010; Stout & Francis 2011). Also, subretinal transplantation of RPE‐choroid sheets was not superior to RPE in suspension and resulted in more postoperative complications in a randomized trial (Falkner‐Radler et al.…”

Section: Cell Suspension Cell Sheets and Scaffoldsmentioning

confidence: 99%

Stem cell‐based treatment in geographic atrophy: promises and pitfalls

Kvanta

Grudzińska

2013

Acta Ophthalmologica

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ABSTRACT. Geographic atrophy is a common and untreatable form of advanced agerelated macular degeneration. The degeneration primarily affects the retinal pigment epithelium and photoreceptors of the retina and their restoration by cell transplantation seems attractive. Recently, a patient with geographic atrophy was the first human to receive cells derived from human embryonic stem cells. In this short review, the rationale, potential and obstacles for stem cellderived therapy in geographic atrophy are discussed.

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Surgical Approaches to Gene and Stem Cell Therapy for Retinal Disease

Cited by 30 publications

References 33 publications

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases

Stem cell‐based treatment in geographic atrophy: promises and pitfalls

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