Levels of Human Tissue Kallikrein in the Vitreous Fluid of Patients with Severe Proliferative Diabetic Retinopathy

Pinna, Antonio; Emanueli, Costanza; Dore, S. E.; Salvo, Marco Michele; Madeddu, Paolo; Carta, Francesco

doi:10.1159/000078617

Cited by 12 publications

(7 citation statements)

References 4 publications

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“…On the other hand, TK is expressed in a wide range of tissues, including the eye [152]. However, it is expressed at a low to non-detectable concentration in the vitreous fluid of patients with proliferative DR, unlike PK, which has a high activity in those patients [153]. PK and TK share a similarity in that upon activation, they both promote the production of highly potent kinin peptides; however, they differ in many aspects such as substrate specificity, tissue distribution, and regulatory mechanisms [154].…”

Section: Microvascular Damage In Drmentioning

confidence: 99%

Diabetic retinopathy: Breaking the barrier

et al. 2017

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Diabetic retinopathy (DR) remains a major complication of diabetes and a leading cause of blindness among adults worldwide. DR is a progressive disease affecting both type I and type II diabetic patients at any stage of the disease, and targets the retinal microvasculature. DR results from multiple biochemical, molecular and pathophysiological changes to the retinal vasculature, which affect both microcirculatory functions and ultimately photoreceptor function. Several neural, endothelial, and support cell (e.g., pericyte) mechanisms are altered in a pathological fashion in the hyperglycemic environment during diabetes that can disturb important cell surface components in the vasculature producing the features of progressive DR pathophysiology. These include loss of the glycocalyx, blood-retinal barrier dysfunction, increased expression of inflammatory cell markers and adhesion of blood leukocytes and platelets. Included in this review is a discussion of modifications that occur at or near the surface of the retinal vascular endothelial cells, and the consequences of these alterations on the integrity of the retina.

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Section: Microvascular Damage In Drmentioning

confidence: 99%

Diabetic retinopathy: Breaking the barrier

et al. 2017

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“…Thus, higher total protein content of vitreous may have contributed to the reported lower kallikrein values in DR vitreous. In contrast to components of the plasma KKS, very low levels of TK were detected in PDR vitreous [37], suggesting that vitreous TK plays little or no role in PDR. The mechanisms that contribute to the appearance of the plasma KKS in the vitreous are not fully understood.…”

Section: In Humansmentioning

confidence: 83%

Plasma Kallikrein and Diabetic Macular Edema

Feener

2010

Curr Diab Rep

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Recent proteomic studies have identified components of the kallikrein kinin system, including plasma kallikrein, factor XII, and kininogen, in vitreous obtained from individuals with advanced diabetic retinopathy. In rodent models, activation of plasma kallikrein in vitreous increases retinal vascular permeability; whereas inhibition of the kallikrein kinin system reduces retinal leakage induced by diabetes and hypertension. These findings suggest that intraocular activation of the plasma kallikrein pathway may contribute to excessive retinal vascular permeability that can lead to diabetic macular edema. The kallikrein kinin system contains two separate and independently regulated serine proteases that generate bradykinin peptides: plasma kallikrein and tissue kallikrein. Tissue kallikrein is expressed in the retina and ciliary body, where it has been implicated in exerting autocrine or paracrine effects via bradykinin receptors that are colocalized in these tissues. Emerging evidence suggests that plasma kallikrein inhibitors may provide a new therapeutic opportunity to reduce retinal vascular permeability.

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“…Through hybridization experiments, TK, LMWK, and the kinin receptors were localized to the inner and outer nuclear layers of the retina as well as the ganglion cell layer. Interestingly, whereas PK activity is high in the vitreous fluid of subjects with proliferative diabetic retinopathy, 16,17 TK is reportedly low to nondetectable in the vitreous fluid of such subjects 26 and is not likely a factor in this form of ocular pathology.…”

Section: Tissue Kallikrein/kinin In Ocular Functionmentioning

confidence: 92%

The Kallikrein/Kinin System in Ocular Function

Webb

2011

Journal of Ocular Pharmacology and Therapeutics

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The kallikrein/kinin system uses two distinct serine proteases, plasma kallikrein and tissue kallikrein, to yield bradykinin and Lys-bradykinin (kallidin) from specific substrate kininogens. The kallikrein/kinin system is known to have a role in contact-activated coagulation mechanisms and in inflammatory responses, and recently has been shown to contribute to homeostatic and protective mechanisms in the cardiovascular and renal systems. This article reviews current knowledge of the ocular kallikrein/kinin system within the context of proposed roles for this system in other important organs and tissues. All components of the kallikrein/kinin system are present in the eye and are positioned to participate in key ocular functions. Plasma kallikrein binds to vascular endothelium and generates bradykinin, which may contribute to regulation of ocular blood flow, and, in excess, has been implicated in the pathogenesis of retinal edema in patients with proliferative diabetic retinopathy. Tissue kallikrein is expressed in retina, ciliary muscle, and trabecular meshwork cells and could be a significant factor in the protective mechanism of ischemic preconditioning, and in the modulation of aqueous dynamics. Improved understanding of the role of plasma and tissue kallikreins and kinins in such processes has the potential to identify significant new targets for the therapy of ocular dysfunction.

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Levels of Human Tissue Kallikrein in the Vitreous Fluid of Patients with Severe Proliferative Diabetic Retinopathy

Cited by 12 publications

References 4 publications

Diabetic retinopathy: Breaking the barrier

Diabetic retinopathy: Breaking the barrier

Plasma Kallikrein and Diabetic Macular Edema

The Kallikrein/Kinin System in Ocular Function

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