Introduction to Intravitreal Delivery

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10.1038/s41434-019-0100-9

We investigated whether adjuvant pharmacological agents may enhance rAAV transduction of the retinas of mouse and rat after intravitreal delivery.

Retina transduction by rAAV2 after intravitreal injection: comparison between mouse and rat

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10.1242/dev.175117

However, stimulation of retinal astrocytic growth by intravitreal delivery of PDGF-A was sufficient to block retinal vascular pruning in wild-type mice.

Developmental vascular pruning in neonatal mouse retinas is programmed by the astrocytic oxygen-sensing mechanism

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10.1038/s41434-019-0089-0

Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth.

Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury

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10.1016/j.exer.2019.107756

Here we show intravitreal delivery of tunicamycin primarily induced ER stress in photoreceptor cells resulting in their loss by apoptosis.

Tunicamycin-induced photoreceptor atrophy precedes degeneration of retinal capillaries with minimal effects on retinal ganglion and pigment epithelium cells.

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10.1007/s40135-019-00194-0

While intravitreal delivery of molecules has been most commonly used, direct targeting of the optic nerve should be considered.

Optic Nerve Regeneration: Considerations on Treatment of Acute Optic Neuropathy and End-Stage Disease

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10.1007/s12035-018-1460-7

APP−/− mice exhibit greater susceptibility to retinal rotenone toxicity, while intravitreal delivery of sAPPα reduces inner retinal neuronal death in wild-type mice following rotenone challenge.

Amyloid Precursor Protein Mediates Neuronal Protection from Rotenone Toxicity

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10.1089/hum.2018.118

Thus, we developed a new human-DNA MiniPromoter, Ple345 (NEFL), which in combination with intravitreal delivery in rAAV9 showed specific and robust expression in the retinal ganglion cells of the nonhuman-primate rhesus macaque retina.

New MiniPromoter Ple345 (NEFL) Drives Strong and Specific Expression in Retinal Ganglion Cells of Mouse and Primate Retina

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10.1016/j.omtm.2018.12.006

This significantly improved AAV-mediated transduction of retinal cells in wild-type mice following intravitreal delivery, with gene expression in retinal pigment epithelium and photoreceptor cells.

Trans-ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Gene Transduction after Intravitreal Vector Administration

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10.1007/s12015-019-09908-0

In this study, we analyzed the immunomodulatory properties of mouse bone marrow-derived MSCs after their intravitreal delivery to the inflammatory environment in the eye, caused by the application of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ.

The Immunomodulatory Potential of Mesenchymal Stem Cells in a Retinal Inflammatory Environment

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10.1167/iovs.19-26936

Both intraperitoneal and intravitreal delivery of Apratoxin S4 are able to impede ocular neovascularization in vivo.

Apratoxin S4 Inspired by a Marine Natural Product, a New Treatment Option for Ocular Angiogenic Diseases.

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10.1016/j.omtm.2019.06.001

Our results demonstrate that intravitreal delivery of sGFP-TatCARD reduces inflammation and can protect the retina from both acute and sustained oxidative damage within the RPE and choroid.

Expression of a CARD Slows the Retinal Degeneration of a Geographic Atrophy Mouse Model

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10.1016/j.ymthe.2018.11.003

ADVM-022, an adeno-associated virus vector encoding aflibercept, is optimized for intravitreal delivery and strong protein expression.

Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration

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Intravitreal Delivery
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What is/are Intravitreal Delivery?

Intravitreal Delivery - We investigated whether adjuvant pharmacological agents may enhance rAAV transduction of the retinas of mouse and rat after intravitreal delivery. [1] However, stimulation of retinal astrocytic growth by intravitreal delivery of PDGF-A was sufficient to block retinal vascular pruning in wild-type mice. [2] Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. [3] Here we show intravitreal delivery of tunicamycin primarily induced ER stress in photoreceptor cells resulting in their loss by apoptosis. [4] While intravitreal delivery of molecules has been most commonly used, direct targeting of the optic nerve should be considered. [5] APP−/− mice exhibit greater susceptibility to retinal rotenone toxicity, while intravitreal delivery of sAPPα reduces inner retinal neuronal death in wild-type mice following rotenone challenge. [6] Thus, we developed a new human-DNA MiniPromoter, Ple345 (NEFL), which in combination with intravitreal delivery in rAAV9 showed specific and robust expression in the retinal ganglion cells of the nonhuman-primate rhesus macaque retina. [7] This significantly improved AAV-mediated transduction of retinal cells in wild-type mice following intravitreal delivery, with gene expression in retinal pigment epithelium and photoreceptor cells. [8] In this study, we analyzed the immunomodulatory properties of mouse bone marrow-derived MSCs after their intravitreal delivery to the inflammatory environment in the eye, caused by the application of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ. [9] Both intraperitoneal and intravitreal delivery of Apratoxin S4 are able to impede ocular neovascularization in vivo. [10] Our results demonstrate that intravitreal delivery of sGFP-TatCARD reduces inflammation and can protect the retina from both acute and sustained oxidative damage within the RPE and choroid. [11] ADVM-022, an adeno-associated virus vector encoding aflibercept, is optimized for intravitreal delivery and strong protein expression. [12]