Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants

Zou, Ling; Hong, Wenting; Tsai, Yi Ting; Hu, Zhibing; Tang, Liping

doi:10.1371/journal.pone.0028720

Cited by 14 publications

(11 citation statements)

References 77 publications

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“…Expression can be detected as early as 4 hours (Losa et al, 1991) and is longer lasting in inner than in outer ocular tissues (Eljarrat-Binstock et al, 2008). Intracameral injection allows transfection of TM (Farjo et al, 2006; Zou et al, 2011). Intravitreal injection of poly (llactic acid), polystyrene, and Poly N-isopropylacrylamide particles caused a substantial reduction of IOP and TM inflammation making hyaluronic acid a better candidate for TM gene delivery (Zou et al, 2011).…”

Section: Non-viral Gene Deliverymentioning

confidence: 99%

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Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

show abstract

Section: Non-viral Gene Deliverymentioning

confidence: 99%

“…Intracameral injection allows transfection of TM (Farjo et al, 2006; Zou et al, 2011). Intravitreal injection of poly (llactic acid), polystyrene, and Poly N-isopropylacrylamide particles caused a substantial reduction of IOP and TM inflammation making hyaluronic acid a better candidate for TM gene delivery (Zou et al, 2011). …”

Section: Non-viral Gene Deliverymentioning

confidence: 99%

Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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“…Homopolymer and copolymer synthesis PNIPAM, copolymer of NIPAM and NT (N 85 NT 15 ), and copolymer of NIPAM and BA (N 95 BA 5 ) were synthesized using free radical polymerization (44,45). For N 85 NT 15 , a solution of NIPAM (4.25 g), NT (0.75 g), and 2,2′-azobisisobutyronitrile (0.021 g) was dissolved in 60 ml of dry tetrahydrofuran (THF).…”

Section: Methodsmentioning

confidence: 99%

A reversible thermoresponsive sealant for temporary closure of ocular trauma

et al. 2017

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Open globe injuries are full-thickness injuries sustained to the eye wall (cornea or sclera), which cause immediate drops in intraocular pressure that may lead to retinal detachment and permanent vision loss if not treated rapidly after injury. The current standard of care for open globe injuries consists of suturing the margins closed, but the technique can be time-consuming, requires specialized training and equipment, and can lead to patient discomfort, abrasion, and infection from eye rubbing. We engineered an injectable, thermoresponsive sealant (TRS) and a custom tool to occlude open globe injuries. The smart hydrogel sealant consists of physically cross-linked -isopropylacrylamide copolymerized with butylacrylate. At low temperatures, it can be injected as a liquid, and when raised to body temperature, a heat-induced gelation converts the hydrogel into a solidified occlusion. The sealant can be repositioned or removed without causing additional trauma via exposure to cold water. In vitro and ex vivo assessments of mechanical adhesion to eye tissue revealed maintenance of intraocular pressure that is five times greater than the physiological range with reversible seal strength comparable to cyanoacrylate (super glue). In vivo assessment in a rabbit model of ocular trauma demonstrated ease of use for TRS deployment, statistically significant improvement in wound sealing, and no evidence of neurotoxicity, retinal tissue degradation, or significant chronic inflammatory response after 30 days of exposure. Given the advantages of body heat-induced gelation, rapid reversible occlusion, and in vivo safety and efficacy, shape-adaptable TRSs have translational potential as smart wound sealants for temporary occlusion of surgical incisions or traumatic injuries.

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“…Expression can be detected as early as 4 hours (Losa et al, 1991) and is longer lasting in inner than in outer ocular tissues (Eljarrat-Binstock et al, 2008). Intracameral injection allows transfection of TM (Farjo et al, 2006; Zou et al, 2011). Intravitreal injection of poly (l-lactic acid), polystyrene, and Poly N-isopropylacrylamide particles caused a substantial reduction of IOP and TM inflammation making hyaluronic acid a better candidate for TM gene delivery (Zou et al, 2011).…”

Section: Non-viral Gene Deliverymentioning

confidence: 99%

“…Intracameral injection allows transfection of TM (Farjo et al, 2006; Zou et al, 2011). Intravitreal injection of poly (l-lactic acid), polystyrene, and Poly N-isopropylacrylamide particles caused a substantial reduction of IOP and TM inflammation making hyaluronic acid a better candidate for TM gene delivery (Zou et al, 2011).…”

Section: Non-viral Gene Deliverymentioning

confidence: 99%

Gene Transfer to the Outflow Tract

Dang

Loewen

Parikh

et al. 2016

Preprint

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Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm′s canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm′s canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

show abstract

Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants

Cited by 14 publications

References 77 publications

Gene transfer to the outflow tract

Gene transfer to the outflow tract

A reversible thermoresponsive sealant for temporary closure of ocular trauma

Gene Transfer to the Outflow Tract

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