In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR–proNGF pathway

Gharbiya, Magda; Sacchetti, Marta; Rosso, Pamela; Carito, Valentina; Segatto, Marco; Fico, Elena; Tirassa, Paola; Lambìase, Alessandro

doi:10.1002/jcp.26806

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…Among the retina trophic factors, the neurotrophin nerve growth factor (NGF) [ 1 , 2 ] and vascular endothelial growth factor A (VEGFA), the first discovered VEGF family member [ 3 , 4 ], have been demonstrated to be pivotally important in supporting functional retinal integrity [ 5 , 6 ]. Altered VEGF/NGF synthesis and/or changes in the expression and activation of their specific receptors; namely, vascular endothelial growth factor 2 (VEGFR2) and tropomyosin-related kinase A (TrkA), respectively, have also been found to contribute to retina degenerative events, involving both the vascular system and the neurons similarly occurring in diabetic retinopathy (DR) [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats

Fico

Rosso

Triaca

et al. 2022

Cells

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Among the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the administration of eye drops containing NGF (ed-NGF) to adult Sprague Dawley rats receiving streptozotocin (STZ) intraperitoneal injection was used as an experimental paradigm to investigate NGF modulation of VEGFA and its receptor VEGFR2 expression. We show that ed-NGF treatment prevents the histological and vascular alterations in STZ retina, VEGFR2 expression decreased in GCL and INL, and preserved the co-expression of VEGFR2 and NGF-tropomyosin-related kinase A (TrkA) receptor in retinal ganglion cells (RGCs). The WB analysis confirmed the NGF effect on VEGFR2 expression and activation, and showed a recovery of VEGF isoform dysregulation by suppressing STZ-induced VEGFA121 expression. Reduction in inflammatory and pro-apoptotic intracellular signals were also found in STZ+NGF retina. These findings suggest that ed-NGF administration might favor neuroretina protection, and in turn counteract the vascular impairment by regulating VEGFR2 and/or VEGFA isoform expression during the early stages of the disease. The possibility that an increase in the NGF availability might contribute to the switch from the proangiogenic/apoptotic to the neuroprotective action of VEGF is discussed.

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Section: Introductionmentioning

confidence: 99%

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats

Fico

Rosso

Triaca

et al. 2022

Cells

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“…Moreover, injection of ranibizumab, an antivascular endothelial growth factor drug has been useful for some patients with macular edema or proliferative disease since it was approved by the FDA in 2017 (5). Unfortunately, the above DR treatments also bring adverse effects and economic burdens to the patients and their families (6). However, little is usable for the early stage of the disease.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 prevents early diabetic retinopathy via reducing retinal ganglion cell layer and inner nuclear layer cell apoptosis in db/db mice

et al. 2020

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Background: Diabetic retinopathy (DR), a diabetic vascular complication, is prone to developing into blindness. Ginsenoside Rg1 (GRg1), a major saponin in ginseng, exerts high anti-apoptotic activity.Methods: This study aimed to explore the protective effects of GRg1 against diabetes-induced retinal damage. Measurements of blood glucose, blood lipids and vascular permeability were performed, as well as assessments of pathological changes, and the retinal thickness of each layer. Retinal cell apoptosis related protein expression levels were measured by immunofluorescence and western blot assays.Results: Our data demonstrated that GRg1 effectively reduced blood glucose and triglyceride levels and maintained normal retinal permeability and physiological structure. GRg1 maintained the thickness of the ganglion cell layer (GCL) and the inner nuclear layer (INL) by reducing cell apoptosis.Conclusions: These data strongly indicate that GRg1 prevents diabetic retinal changes by decreasing GCL and INL cell apoptosis. GRg1 may be a promising drug for early DR treatment.

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“…Treatment of wet AMD requires repeated intravitreal injections, and intravitreal agents are eliminated from the eye almost exclusively via the aqueous humor outflow, so the accompanying risk of corneal endothelium impairment should be considered. ere are few reports involving the influence of intracameral aflibercept and ranibizumab on the corneal endothelium [19][20][21]. Ari et al examined the effect of intracameral ranibizumab on the rabbit corneal endothelium by scanning electron microscopy [21].…”

Section: Discussionmentioning

confidence: 99%

“…ey observed the deterioration in endothelial cell morphology after intracameral injection of 1 and 0.5 mg ranibizumab. Gharbiya et al demonstrated that anterior chamber injection of two different anti-VEGF agents, aflibercept and ranibizumab, affects the rabbit corneal endothelium in terms of survival and apoptosis and is associated with changes in the endothelial expression of the NGF precursor (proNGF) and p75 neurotrophin receptor (p75NTR) [19]. On the contrary, Wilhelm et al observed that ranibizumab and bevacizumab have no damaging effects on the corneal endothelium after injection into the anterior chamber in a porcine eye model [20].…”

Section: Discussionmentioning

confidence: 99%

Effect of Repeated Intravitreal Ranibizumab and Aflibercept Injections on the Cornea in Patients with Age-Related Macular Degeneration

Urban

Szwabowicz²,

Bakunowicz-Łazarczyk

2020

Journal of Ophthalmology

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Purpose. To assess the effect of repeated intravitreal ranibizumab injections (RI) and aflibercept injections (AI) on the corneal endothelium and central corneal thickness (CCT) in patients with age-related macular degeneration (AMD). Materials and Methods. In the retrospective study, 110 eyes of 106 patients, aged 52 to 93 years, were analyzed. Fifty eyes were treated only with RI (I group), and 60 eyes were treated only with AI (II group). Every patient received one intravitreal injection of 0.5 mg of ranibizumab once a month or 2 mg of aflibercept for 3 subsequent months. Each patient received only 3 injections during the whole observation period. Corneal analysis was obtained with the specular microscope. Examinations were performed before initial treatment, after each injection, and 6 months after the first injection. Analysis included corneal endothelial cell density (ECD), hexagonal cell percentage (% Hex), coefficient of variation (CoV), and CCT. Results. There was a statistically significant ECD loss, regardless of the type of the anti-VEGF agent. The mean ECD value in the I group was 2397 ± 459 cells/mm2 before RI, 2389 ± 459 cells/mm2 after the first RI, 2386 ± 467 cells/mm2 after the second RI, 2378 ± 475 cells/mm2 after the third RI, and 2357 ± 460 cells/mm2 6 months after the first RI. The mean ECD value in the II group was 2448 ± 493 cells/mm2 before treatment, 2456 ± 498 cells/mm2 after the first AI, 2426 ± 496 cells/mm2 after the second AI, 2402 ± 488 cells/mm2 after the third AI, and 2348 ± 473 cells/mm2 6 months after the first AI. In comparison with the group treated with RI, the group treated with AI presented a greater ECD loss at each measuring point. The percentage of hexagonal cells was decreased in both groups. There was a slight increase in polymegathism in both treated groups. Ranibizumab proved to cause a small increase in CCT, while CCT remained unchanged in the aflibercept group. Conclusions. Repeated intravitreal injections of 0.5 mg of ranibizumab or 2 mg of aflibercept can influence the morphology of the corneal endothelium but not CCT.

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In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR–proNGF pathway

Cited by 8 publications

References 44 publications

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats

Ginsenoside Rg1 prevents early diabetic retinopathy via reducing retinal ganglion cell layer and inner nuclear layer cell apoptosis in db/db mice

Effect of Repeated Intravitreal Ranibizumab and Aflibercept Injections on the Cornea in Patients with Age-Related Macular Degeneration

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