Association of Anti-VEGF Injections with Progression of Geographic Atrophy

Enslow, Ryan; Bhuvanagiri, Sai; Vegunta, Sravanthi; Cutler, Benjamin; Neff, Michael

doi:10.4137/oed.s38863

Cited by 22 publications

(19 citation statements)

References 14 publications

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“…No treatments are available for avAMD. The two major limitations of anti-VEGFs are the lack of improvement of vision in 60-70% of patients and adverse effects (Nesmith et al, 2014) including more rapid progression of GA (Enslow et al, 2016), increased intraocular pressure, retinal detachment, endophthalmitis, photoreceptor cell death and thinning of the inner neuronal layer of the retina (Saint-Geniez et al, 2008;Scott & Bressler, 2013). In addition to the adverse effects, the issues associated with logistics of blind or low-vision patients traveling to a clinic on a monthly basis result in a significant number of patients discontinuing treatment, which has been reported to be from 57% over five years (Boulanger-Scemama et al, 2015) to as high as 71% within 24 months (Lad et al, 2014).…”

Section: Amd Is a Major Cause Of Acquired Irreversible Blindness In Amentioning

confidence: 99%

Going non-viral: theSleeping Beautytransposon system breaks on through to the clinical side

Hudecek

Izsvák

Johnen

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

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Molecular medicine has entered a high-tech age that provides curative treatments of complex genetic diseases through genetically engineered cellular medicinal products. Their clinical implementation requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective and economically viable manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient non-viral gene delivery approaches that are prevalent in ongoing pre-clinical and translational research. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representing a highly attractive gene transfer strategy for clinical use. Here we review several recent refinements of the system, including the development of optimized transposons and hyperactive SB variants, the vectorization of transposase and transposon as mRNA and DNA minicircles (MCs) to enhance performance and facilitate vector production, as well as a detailed understanding of SB's genomic integration and biosafety features. This review also provides a perspective on the regulatory framework for clinical trials of gene delivery with SB, and illustrates the path to successful clinical implementation by using, as examples, gene therapy for age-related macular degeneration (AMD) and the engineering of chimeric antigen receptor (CAR)-modified T cells in cancer immunotherapy.

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Section: Amd Is a Major Cause Of Acquired Irreversible Blindness In Amentioning

confidence: 99%

Going non-viral: theSleeping Beautytransposon system breaks on through to the clinical side

Hudecek

Izsvák

Johnen

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

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“…Although the current treatment of AMD with intravitreal anti-VEGF injection offers new hope to thousands of patients with neovascular AMD, there are risks of adverse effects, including severe atrophy of choriocapillaris due to repeated treatment. [36][37][38] In contrast, targeting macrophages to blunt excessive VEGF upregulation can be a promising strategy in CNV therapy. A previous report showed that inhibition of M2type macrophage polarization by doxycycline as an alternative therapeutic approach against long-term anti-VEGF treatments, attenuated IL-1b-induced pathological blood vessel growth.…”

Section: Discussionmentioning

confidence: 99%

Lactic Acid Upregulates VEGF Expression in Macrophages and Facilitates Choroidal Neovascularization

Song

Lee

Park

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…PBMC from the patients who had MA produced increased levels of VEGF. Previous studies have shown that enhanced MA progression in nAMD patients is associated with anti-VEGF injections [ 52 ]. In the present study, a numerically greater proportion of patients with MA had received more anti-VEGF injections than those without but this did not reach statistical significance ( P = 0.056).…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8)

Lechner

Chen

Hogg

et al. 2017

J Neuroinflammation

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BackgroundInfiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy.MethodsOne hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25–30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay.ResultsPBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11b+CD3− monocytes. The percentage of CD11b+CD3− IL-8+ was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level of CCL2 was not increased in nAMD patients although there was a trend of increased IL-8 in nAMD patients.ConclusionsPBMCs, in particular monocytes, may contribute to CNV development in nAMD through secreting elevated levels of IL-8, CCL2 and VEGF after they are recruited to the macula. Apart from VEGF, IL-8 and CCL2 may be additional targets for nAMD management.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0820-y) contains supplementary material, which is available to authorized users.

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Association of Anti-VEGF Injections with Progression of Geographic Atrophy

Cited by 22 publications

References 14 publications

Going non-viral: theSleeping Beautytransposon system breaks on through to the clinical side

Going non-viral: theSleeping Beautytransposon system breaks on through to the clinical side

Lactic Acid Upregulates VEGF Expression in Macrophages and Facilitates Choroidal Neovascularization

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8)

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