Plasminogen in proliferative vitreoretinal disorders

Abstract

Objective-Intravitreal fibrin formation is a frequent observation after vitrectomy performed for a variety of vitreoretinal disorders including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and endophthalmitis. Plasminogen activators (PA) have been used for the management of this postoperative complication. This approach requires the presence of plasminogen, the substrate for PA mediated fibrinolysis, in the vitreal cavity. Methods-Quantification of plasminogen in the vitreous of 60 patients with PVR, PDR, and macular pucker was performed by streptokinase mediated activation using a chromogenic substrate. The presence of immunoreactive plasminogen was confirmed by immunoblot analysis of vitreal proteins and immunocytochemistry of surgically removed epiretinal membranes. Results-Plasminogen levels were dramatically increased in the vitreous of PVR and PDR patients compared with macular pucker patients and normal controls. Staining for plasminogen in epiretinal membranes was confined to the extracellular matrix. Predominant staining of perivascular areas in PDR specimens indicated that breakdown of the bloodretinal barrier is an important source of intravitreal plasminogen in that condition. Conclusion-Plasminogen may play a role in traction membrane formation in PVR and PDR. Our biochemical analysis of presurgical vitreous indicates that there may be abundant substrate for PA mediated fibrinolysis in the vitreous cavity after vitrectomy. (Br J Ophthalmol 1997;81:590-594)

Intravitreal Functional Plasminogen Is Elevated in Central Retinal Vein Occlusion

“…The mean plasminogen activity was shown to be 2.19 ± 1.89%N and we attribute these results to the BRB breakdown secondary to CRVO (‘leaky eyes'). Those results are in accordance with observations by Esser et al [63], who demonstrated an increase in intravitreal plasminogen activities along with the increase in total intraocular protein, which serves as a marker for BRB breakdown in patients with proliferative vitreoretinopathy and proliferative diabetic vitreoretinopathy. They consequently attributed the source of intraocular plasminogen to the development of BRB breakdown.…”

“…In general, a BRB breakdown results in elevated intraocular levels of various proteins due to a passover of the latter from the plasma to the vitreous cavity. This relationship has been demonstrated for various plasma proteins and cytokines like albumin, transferrin, immunoglobulins and VEGF in the past [18,57,58,59,60,61]. As a conclusion we postulate that beside those substrates intravitreal plasminogen might be elevated as well in patients with CRVO (fig.…”

“…Ulrich et al [62] were not able to detect any plasminogen activity in vitreous samples in patients with and without BRB breakdown. In contrast, Esser et al [63] found a significant increase in vitreous plasminogen activities in patients with proliferative (diabetic) vitreoretinopathy (0.108-0.142 mg/ml; about 100%N) with a consecutive BRB breakdown in comparison to healthy controls (0.015 mg/ml; about 1%N), and plasminogen activities were correlated with the severity of diabetic vitreoretinal damage.…”

“…However, the source of this basal plasminogen activity remains unknown, because in eyes with no BRB breakdown plasminogen might not have the potential to cross the intact inner BRB [18]. In contrast, an intraocular source of plasminogen has not been described so far [63]. Further investigations have to clarify this open question.…”

Plasminogen activators promote excitotoxicity‐induced retinal damage

“…In a clinical setting, tPA has been used to treat stroke patients (48,49), as well as patients with submacular hemorrhage (50)(51)(52)(53)(54). Although the functional roles of these proteases in the retina are unclear, mounting evidence indicates that tPA and uPA might play a degenerative role in the CNS (30)(31)(32)(55)(56)(57)(58)(59)(60) and retina (42,(61)(62)(63)(64).…”