a-step-by-step-protocol-for-subretinal-surgery-in-rabbits

A Step by Step Protocol for Subretinal Surgery in Rabbits

Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in ...

retinal-pigment-epithelium-transplantation-non-human-primate-model

Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases

Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These ...

University of Bonn

National University of Singapore

Agency for Science, Technology and Research (A*STAR)

Singapore Eye Research Institute (SERI)

To evaluate the influence of surface topography on the proliferation of the retinal pigment epithelium (RPE) by comparing nanofibrillar and smooth substrates.

A nanofibrillar surface promotes superior growth characteristics in cultured human retinal pigment epithelium.

To develop a surgical technique for the subretinal implantation of cell carriers suitable for the transplantation of cultured retinal pigment epithelium (RPE) in a preclinical animal model.

Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation.

To investigate intraocular concentrations and pharmacokinetics of ranibizumab after a single intravitreal injection in humans.

Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans.

Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application.

Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

To assess tight junction integrity in cultured human foetal retinal pigment epithelium (RPE) after exposure to clinically relevant indocyanine green (ICG) concentrations.

Indocyanine green concentrations used in chromovitrectomy cause a reversible functional alteration in the outer blood-retinal barrier.

To assess tight junction (TJ) integrity in cultured human fetal retinal pigment epithelium (HFRPE) after exposure to clinically relevant novel vital dyes.

Effect of novel vital dyes on outer blood-retina barrier function in cultured human retinal pigment epithelium.

Tissue engineered retinal pigment epithelial (RPE) transplantation is a promising cell-based therapy for age-related macular degeneration. The aim of this work is to develop a supportive scaffold with a favorable topography to aid functional RPE monolayer maintenance while being tolerated underneath the retina. To this end, films and electrospun substrates with fiber diameters ranging from 200 to 1000 nm were made of polyethylene terephthalate or poly(L-lactide-co-ε-caprolactone), and then tested using human fetal RPE cells in vitro and transplanted subretinally in rabbits. The results indicated that RPE on both 200 nm fiber variants showed the highest cell densities, adherent monolayers achieved deeper pigmentation, and more uniform hexagonal tight junctions. Facile subretinal implantation of flat 200 nm fiber membranes was achieved by electrospinning them onto a porous rigid-elastic carrier. Spectral-domain optical coherence tomography showed a reattached, slightly thinned retina overlying the implants over 2 weeks observation. Histology demonstrated native RPE variably migrated onto the nanofibers, and a reactive gliosis with some photoreceptor degeneration. In conclusion, scaffolds with 200 nm fiber topography enhanced RPE culture, showed subretinal biocompatibility, and should thus be considered for future cell-based therapies in blinding retinal diseases.

Enhancement of retinal pigment epithelial culture characteristics and subretinal space tolerance of scaffolds with 200 nm fiber topography.

Transplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies.

Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space.

To investigate the geometry, penetration force, and cutting profile of the novel and old needle of the drug delivery system (DDS) for Ozurdex injections in a standardized laboratory setting.

Penetration force, geometry, and cutting profile of the novel and old Ozurdex needle: the MONO study.

To investigate the geometry, penetration force, and cutting profile of 23-gauge trocar systems for pars plana vitrectomy based on their grinding methods in a standardized laboratory setting.

Geometry, penetration force, and cutting profile of different 23-gauge trocars systems for pars plana vitrectomy.

The advantage of intravitreal injections is an immediate and increased therapeutic effect in the intended retinal tissue. The accuracy, precision and reproducibility of the delivered volume depend on the size of the syringe and the physician's manual experience. The eyelids and eyelashes are usually disinfected using a povidone-iodine solution (10%); a sterile speculum is placed and drops of povidone-iodine (5%) are applied. The use of adequate anesthetic topical lidocaine 2% is required. The injection site should be located 3.5-4 mm posterior to the limbus. The angle of the incision through the sclera may be directed in an oblique fashion of 30°. The diameter of the needle should be smaller than 25 G, and the injected volume should be limited to 0.15 ml without a routine paracentesis. The incidence of lens injury is 0.006% (2/32,318) and 0.013% (5/35,942) for rhegmatogenous retinal detachments. The rate of suspected endophthalmitis is 0.018% after bevacizumab and 0.027% after ranibizumab injections. Sterile inflammations have been observed after Avastin injections. The concentrations of vascular endothelial growth factor inhibitors decline in a monoexponential fashion. The half-life of unbound bevacizumab is 9.82 days and that of ranibizumab 7.19 days.

Routes for Drug Delivery to the Eye and Retina: Intravitreal Injections.

We developed a surgical method for localized and atraumatic removal of the retinal pigment epithelium (RPE) with a novel instrument.

ArticleTotal : 2	Year
Publication title Cited by 30	2016
Publication title Cited by 8	2021

Article	Year
A nanofibrillar surface promotes superior growth characteristics in cultured human retinal pigment epithelium. Ophthalmic research\| PubMed ID: 21336003	2011
Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation. Investigative ophthalmology & visual science\| PubMed ID: 22167099	2012
Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. American journal of ophthalmology\| PubMed ID: 22818800	2012
Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera. Retina (Philadelphia, Pa.)\| PubMed ID: 23060033	2012
Indocyanine green concentrations used in chromovitrectomy cause a reversible functional alteration in the outer blood-retinal barrier. Acta ophthalmologica\| PubMed ID: 23889821	2014
Effect of novel vital dyes on outer blood-retina barrier function in cultured human retinal pigment epithelium. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde\| PubMed ID: 24022717	2013
Enhancement of retinal pigment epithelial culture characteristics and subretinal space tolerance of scaffolds with 200 nm fiber topography. Biomaterials\| PubMed ID: 24439407	2014
Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space. Stem cell reports\| PubMed ID: 24511471	2014
Penetration force, geometry, and cutting profile of the novel and old Ozurdex needle: the MONO study. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics\| PubMed ID: 24801111	2014
Geometry, penetration force, and cutting profile of different 23-gauge trocars systems for pars plana vitrectomy. Retina (Philadelphia, Pa.)\| PubMed ID: 25046392	2014
Routes for Drug Delivery to the Eye and Retina: Intravitreal Injections. Developments in ophthalmology\| PubMed ID: 26501462	2016
Localized RPE Removal with a Novel Instrument Aided by Viscoelastics in Rabbits. Translational vision science & technology\| PubMed ID: 27294010	2016

Zengping Liu

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