The kallikrein system in retinal damage/protection

Masuda, Tomomi; Shimazawa, Masamitsu; Hara, Hideaki

doi:10.1016/j.ejphar.2014.10.007

Cited by 13 publications

(6 citation statements)

References 28 publications

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“…Carbazochrome sodium sulfonate hydrate and kallidinogenase are administered for minor retinal hemorrhage. [ 13 ] The retinal hemorrhage in the present patient was sufficiently minor to require only observation after withdrawing the regorafenib. In cases of vascular leakage, intravitreal injection of anti-VEGF antibody is considered.…”

Section: Discussionmentioning

confidence: 75%

Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

Tsuchihashi¹,

Shimokawa

Takayoshi

et al. 2017

Medicine

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Rationale:Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known.Patient concerns:Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction.Diagnoses:Fundus examination revealed hemorrhage of the retinal vein.Interventions:Regorafenib treatment was discontinued and observational therapy was pursued.Outcomes:Retinal and gastrointestinal hemorrhage resolved in 1 week.Lessons:Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified.

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Section: Discussionmentioning

confidence: 75%

Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

Tsuchihashi¹,

Shimokawa

Takayoshi

et al. 2017

Medicine

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“…Although selective inhibition of B1R could potentially provide some protective effect for retinal dysfunction in DR, this approach would not address the potential contributions of B2R or effects mediated by PKal substrates other than HK (18,29). However, the blockade of PKal could reduce the proinflammatory effects of the intravitreal KKS while preserving the potential beneficial ocular effects of BK generated by tissue kallikrein (Klk1) (48). …”

Section: Discussionmentioning

confidence: 99%

Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular Edema

et al. 2015

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This study characterizes the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examines mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P < 0.0001), respectively, in vitreous from subjects with DME compared with those with a macular hole (MH). While the vascular endothelial growth factor (VEGF) level was also increased in DME vitreous, PKal and VEGF concentrations do not correlate (r = 0.266, P = 0.112). Using mass spectrometry–based proteomics, we identified 167 vitreous proteins, including 30 that were increased in DME (fourfold or more, P < 0.001 vs. MH). The majority of proteins associated with DME displayed a higher correlation with PPK than with VEGF concentrations. DME vitreous containing relatively high levels of PKal and low VEGF induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening in mice was not affected by blockade of VEGF receptor 2. Diabetes-induced RVP was decreased by up to 78% (P < 0.001) in Klkb1 (PPK)-deficient mice compared with wild-type controls. B2- and B1 receptor–induced RVP in diabetic mice was blocked by endothelial nitric oxide synthase (NOS) and inducible NOS deficiency, respectively. These findings implicate the PKal pathway as a VEGF-independent mediator of DME.

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“…Our previous study also showed that the expression of vascular endothelial growth factor (VEGF) significantly declined in SHR retinal layers following the increase of blood pressure, suggesting a mechanism responsible for the developmental disabilities of retinal vascularity (Chan et al, ). VEGF can be cleaved by tissue‐derived kallikrein, so the latter has an effect on the disease involving VEGF production (Masuda et al, ). So far, research is still lacking on the rat retinal vascular pattern changes caused by chronic ischemia following the BCCAO procedure.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Common Carotid Artery Occlusion in Spontaneously Hypertensive Rats: A Feasible Animal Model for Ocular Ischemic Syndrome

Wang¹,

Fan

Zhang

et al. 2016

The Anatomical Record

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The purpose of this study was to investigate the feasibility of inducing ocular ischemic syndrome in spontaneously hypertensive rats. Hypertensive and normotensive Wistar-Kyoto rats had bilateral occlusion or sham surgery. They were divided into 4 groups: (1) hypertensive-ischemia, (2) hypertensive-sham, (3) normotensive-ischemia, and (4) normotensive-sham. Four months after the operation, the global changes of the eye and pupillary light reflex were assessed. Then each rat was perfused, and randomly one of the bulbuses oculi was prepared as retinal flat mounts for investigation of vascular changes. The opposite eyeball was prepared as a paraffin section for observation of the linear density of retinal ganglion cells and for thickness measurement. One hypertensive-ischemia rat had a cataract in one eye and another rat in the same group had bulbus oculi collapse in one eye. The light reflex disappeared in 13.33% of hypertensive-ischemia rats, and the rest of the hypertensive-ischemia rats and normotensive-ischemia rats had slow reflex. Compared with the respective controls, the peripheral retinal vascular network in hypertensive-ischemia and normotensive-ischemia rats was sparse; linear density of the retinal ganglion cells was significantly reduced; and the retinal thickness was reduced.

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The kallikrein system in retinal damage/protection

Cited by 13 publications

References 28 publications

Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular Edema

Bilateral Common Carotid Artery Occlusion in Spontaneously Hypertensive Rats: A Feasible Animal Model for Ocular Ischemic Syndrome

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