Vitreous leptin levels in retinal disease

Maberley, David; Cui, J. Z.; Matsubara, Joanne A.

doi:10.1038/sj.eye.6702011

Cited by 25 publications

(15 citation statements)

References 9 publications

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“…In addition, the study suggested that locally produced leptin, not simply leptin derived form circulation, could be involved in the pathogenesis of PDR and RD [31]. Similarly, a small study confirmed higher vitreous leptin levels in PDR relative to other retinopathies [32]. On the other hand, other preliminary analysis involving 25 patients with PDR demonstrated that intravitreous leptin was not directly associated with the disease [33].…”

Section: Introductionmentioning

confidence: 99%

Exploring Leptin Antagonism in Ophthalmic Cell Models

et al. 2013

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BackgroundEmerging evidence suggests that angiogenic and pro-inflammatory cytokine leptin might be implicated in ocular neovascularization. However, the potential of inhibiting leptin function in ophthalmic cells has never been explored. Here we assessed mitogenic, angiogenic, and signaling leptin activities in retinal and corneal endothelial cells and examined the capability of a specific leptin receptor (ObR) antagonist, Allo-aca, to inhibit these functions.Methods and ResultsThe experiments were carried out in monkey retinal (RF/6A) and bovine corneal (BCE) endothelial cells. Leptin at 50-250 ng/mL stimulated the growth of both cell lines in a dose-dependent manner. The maximal mitogenic response (35±7 and 27±3% in RF6A and BCE cells, respectively) was noted at 24 h of 250 ng/mL leptin treatments. Leptin-dependent proliferation was reduced to base levels with 10 and 100 nM Allo-aca in BCE and RF6A cells, respectively. In both cell lines, leptin promoted angiogenic responses, with the maximal increase in tube formation (163±10 and 133±8% in RF6A and BCE cultures, respectively) observed under a 250 ng/mL leptin treatment for 3 h. Furthermore, in both cell lines 250 ng/mL leptin modulated the activity or expression of several signaling molecules involved in proliferation, inflammatory activity and angiogenesis, such as STAT3, Akt, and ERK1/2, COX2, and NFκB. In both cell lines, leptin-induced angiogenic and signaling responses were significantly inhibited with 100 nM Allo-aca. We also found that leptin increased its own mRNA and protein expression in both cell lines, and this autocrine effect was abolished by 100-250 nM Allo-aca.ConclusionsOur data provide new insights into the role of leptin in ocular endothelial cells and represent the first original report on targeting ObR in ophthalmic cell models.

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Section: Introductionmentioning

confidence: 99%

Exploring Leptin Antagonism in Ophthalmic Cell Models

et al. 2013

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“…42 A total of 24 human vitreous samples (12 non-PVR and 12 PVR) were obtained, with individual sample volumes ranging from 0.6 to 1.3 mL. Samples came from two independent sources: 12 (6 PVR and 6 non-PVR) from patient donors at the Ocular Angiogenesis Group, Department of Ophthalmology Academic Medical Center in Meibergdreef, Amsterdam; and 12 (6 PVR and 6 non-PVR) from patient donors at the Vancouver Hospital in association with the University of British Columbia.…”

Section: Patient Vitreousmentioning

confidence: 99%

A Novel Strategy to Develop Therapeutic Approaches to Prevent Proliferative Vitreoretinopathy

Pennock

Rhéaume

Mukai

et al. 2011

The American Journal of Pathology

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Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor ␣ (PDGFR␣) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental PVR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neutralizing a subset of these agents in rabbit vitreous eliminated their ability to induce PVRrelevant signaling and cellular responses. A single intravitreal injection of neutralizing reagents for this subset prevented experimental PVR. To identify growth factors and cytokines likely driving PVR in humans, we subjected vitreous from patients with or without PVR to a similar series of analyses. This analysis accurately identified those agents required for vitreousinduced contraction of cells from a patient PVR membrane. We conclude that combination therapy encompassing a subset of vitreal growth factors and cytokines is a potential approach to prevent PVR. (Am J Pathol

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“…All subjects underwent a standard three-port vitrectomy, with a core sample of vitreous (1.0 to 1.5 ml) taken before initiating the pars plana infusion as described previously. 26 Undiluted samples were divided into aliquots and stored at Ϫ80°C until use.…”

Section: Rabbit Model For Pvrmentioning

confidence: 99%

N-Acetylcysteine Suppresses Retinal Detachment in an Experimental Model of Proliferative Vitreoretinopathy

Lei

Velez

Cui

et al. 2010

The American Journal of Pathology

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Proliferative vitreoretinopathy (PVR) is a complication that develops in 5% to 10% of patients who undergo surgery to correct a detached retina. The only treatment option for PVR is surgical intervention, which has a limited success rate that diminishes in patients with recurring PVR. Our recent studies revealed that antioxidants prevented intracellular signaling events that were essential for experimental PVR. The purpose of this study was to test whether N-acetyl-cysteine (NAC) , an antioxidant used in a variety of clinical settings , was capable of protecting rabbits from PVR. Vitreous-driven activation of PDGFR␣ and cellular responses intrinsic to PVR (contraction of collagen gels and cell proliferation) were blocked by concentrations of NAC that were well below the maximum tolerated dose. Furthermore, intravitreal injection of NAC effectively protected rabbits from developing retinal detachment, which is the sight-robbing phase of PVR. Finally, these observations with an animal model appear relevant to clinical PVR because NAC prevented human PVR vitreous-induced contraction of primary RPE cells derived from a human PVR membrane. Our observations demonstrate that antioxidants significantly inhibited experimental PVR , and suggest that antioxidants have the potential to function as a PVR prophylactic in patients undergoing retinal surgery to repair a detached retina.

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Vitreous leptin levels in retinal disease

Cited by 25 publications

References 9 publications

Exploring Leptin Antagonism in Ophthalmic Cell Models

Exploring Leptin Antagonism in Ophthalmic Cell Models

A Novel Strategy to Develop Therapeutic Approaches to Prevent Proliferative Vitreoretinopathy

N-Acetylcysteine Suppresses Retinal Detachment in an Experimental Model of Proliferative Vitreoretinopathy

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