Expression of cytokines on the iris of patients with neovascular glaucoma

Hou, Xianru; Miao, Heng; Tao, Yong; Li, Xiaoxin; Wong, Ian Y.

doi:10.1111/aos.12510

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…Thus, there are many different retinal gene therapy strategies in the pipeline, including gene augmentation, knockdown, gene editing, delivery of neurotrophic factors, and delivery of reagents, which modulate pathways controlling oxidative stress, neovascularization, or metabolism. [23][24][25][26][27] In addition, there has been an expansion of the ''vector toolkit,'' with the goal of enhancing and facilitating delivery of gene-based treatments to the appropriate cell types and through different delivery routes. [28][29][30][31][32] Proof-of-concept studies in mouse models have shown that some of these vectors can be used to treat different inherited retinal degenerative diseases using gene augmentation or optogenetic strategies and through different routes of delivery.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ciliary body transduction may be useful for delivering stable supplies of diffusible molecules that could be used to treat a variety of different diseases, including wet AMD, and AAV7m8 could be useful in strategies involving diffusible agents such as neurotrophic factors, antioxidants, nutrients, antibodies, or even compounds that could modulate intraocular pressure. [23][24][25][26] Transduction of these structures, however, could also have an impact on safety. It is possible that transduction of anterior segment structures is partially responsible for immunologic/inflammatory sequelae that were apparent after high-dose IVI of AAV7m8.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina

et al. 2017

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Within the next decade, we will see many gene therapy clinical trials for eye diseases, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in preclinical mouse studies. Because there are numerous anatomic and physiologic differences between the eyes of mice and "men" and because surgical delivery approaches and immunologic responses also differ between these species, this study evaluated the transduction characteristics of two promising new serotypes, AAV7m8 and AAV8BP2, in the retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, transduction by both serotypes in the anterior chamber of the eye and the optic pathway of the brain was observed post-intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared with AAV7m8, even at the highest doses administered. These studies underscore the differences in AAV transduction between mice and primates, highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving to clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina

et al. 2017

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“…[2,3] The mechanism underlying NVG in proliferative DR (PDR) is mainly mediated by various cytokines and enzymes induced by retinal ischemia and inflammation. [4,5] The most suspected and studied cytokine is vascular endothelial growth factor (VEGF), and anti-VEGF agents have been used to treat various diseases involving retinal ischemic conditions such as PDR. [6] Treatments for PDR patients, including panretinal photocoagulation (PRP), vitrectomy, and anti-VEGF agents, are targeted to reduce cytokine levels in the vitreous.…”

Section: Introductionmentioning

confidence: 99%

Neovascular glaucoma after vitrectomy in patients with proliferative diabetic retinopathy

Kwon

Jee²,

La³

2017

Medicine

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To evaluate the prevalence and risk factors of neovascular glaucoma (NVG) after vitrectomy in patients with vitreous hemorrhage associated with proliferative diabetic retinopathy (PDR). This retrospective, noncomparative, observational study included 127 eyes of 127 patients with PDR who received vitrectomy with a follow-up period of at least 6 months. The prevalence of NVG and associated risk factors were assessed including sex, age, previous panretinal photocoagulation, baseline intraocular pressure, combined phacovitrectomy, and pretreatment with intravitreal bevacizumab (IVB) before vitrectomy for the treatment of vitreous hemorrhage. NVG developed in 15 (11.8%) of 127 patients. Of the 15 eyes with NVG, 11 cases (73.3%) postoperatively developed NVG within 6 months. Postoperative NVG was associated with preoperative IVB treatment (odds ratio, 4.43; P = 0.019). The prevalence of NVG after vitrectomy was 11.8%, and an associated risk factor for NVG was preoperative IVB for the treatment of vitreous hemorrhage.

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“…Accumulating evidence has suggested that inflammatory processes play a major role in the pathogenesis of DR, 4 , 5 neovascular glaucoma (NVG) associated with DR, 6 and age-related macular degeneration. 7 Studies including ours 8 , 9 have demonstrated that MCP-1, IL-6, IL-8, and VEGF are the 4 major inflammatory cytokines that are upregulated in eyes with PDR.…”

Section: Introductionmentioning

confidence: 99%

Differential association of elevated inflammatory cytokines with postoperative fibrous proliferation and neovascularization after unsuccessful vitrectomy in eyes with proliferative diabetic retinopathy

Kobayashi¹,

Nakao²,

Sassa³

et al. 2017

OPTH

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BackgroundPars plana vitrectomy is the only treatment for advanced proliferative diabetic retinopathy (PDR). However, vitrectomy is not always successful despite current progress in vitreoretinal surgical techniques. The aim of our study was to investigate whether the vitreal concentrations of MCP-1, IL-6, IL-8, and VEGF are elevated after unsuccessful vitrectomy in patients with PDR and to investigate whether the altered levels of these cytokines are associated with the cause for the reoperation.Patients and methodsVitreous samples were collected from 263 eyes of 233 patients: PDR (n=129 eyes), proliferative vitreoretinopathy (PVR; n=24 eyes) and nondiabetic controls (n=110 eyes) prior to vitrectomy. Vitreous samples were also collected from 14 eyes of 14 patients with PDR before vitrectomy and from the same 14 eyes before a second vitrectomy for reoperation. The levels of MCP-1, IL-6, IL-8, and VEGF were measured by flow cytometry using a cytometric bead array (CBA) assay.ResultsThe mean concentrations of vitreal MCP-1, IL-6, IL-8, and VEGF were significantly higher in patients with PDR and PVR (P<0.01). There were significantly high correlations among the concentrations of MCP-1, IL-6, and IL-8, whereas the correlation of VEGF with the other 3 cytokines was lower. Among the 14 patients who required reoperation, the mean vitreal concentrations of MCP-1, IL-6, and IL-8 were higher than that at the time of the initial vitrectomy (P<0.01). At the time of the reoperation vitrectomy, the mean vitreous level of MCP-1, IL-6, and IL-8 in eyes with fibrous proliferation was higher than in those without fibrous proliferation (P<0.05). In contrast, VEGF in eyes with neovascular glaucoma (NVG) or anterior hyaloidal fibrovascular proliferation (AHFVP) was higher than in the eyes without NVG and AHFVP (P<0.05).ConclusionThe elevated levels of MCP-1, IL-6, and IL-8 may be the cause of the postoperative fibrous proliferation. In contrast, VEGF may be the cause of the neovascularization after unsuccessful vitrectomy in the eyes of PDR patients.

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Expression of cytokines on the iris of patients with neovascular glaucoma

Cited by 16 publications

References 42 publications

Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina

Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina

Neovascular glaucoma after vitrectomy in patients with proliferative diabetic retinopathy

Differential association of elevated inflammatory cytokines with postoperative fibrous proliferation and neovascularization after unsuccessful vitrectomy in eyes with proliferative diabetic retinopathy

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