The uPAR System as a Potential Therapeutic Target in the Diseased Eye

被引:26
作者
Cammalleri, Maurizio [1 ]
Dal Monte, Massimo [1 ]
Pavone, Vincenzo [2 ]
De Rosa, Mario [3 ]
Rusciano, Dario [4 ]
Bagnoli, Paola [1 ]
机构
[1] Univ Pisa, Dipartimento Biol, I-56127 Pisa, Italy
[2] Univ Napoli Federico II, Dipartimento Sci Chim, I-80126 Naples, Italy
[3] Univ Campania, Dipartimento Med Sperimentale, I-80138 Naples, Italy
[4] Sooft Italia SpA, Contrada Molino 17, I-63833 Montegiorgio, FM, Italy
关键词
ocular diseases; animal models; angiogenesis; inflammation; vascular leakage; photoreceptor degeneration; retinal function; co-receptor signaling; uPAR system blockade; UROKINASE PLASMINOGEN-ACTIVATOR; FORMYL PEPTIDE RECEPTORS; BLOOD-RETINAL BARRIER; GROWTH-FACTOR VEGF; TUMOR-INDUCED ANGIOGENESIS; DIABETIC MACULAR EDEMA; MOUSE MODEL; CHOROIDAL NEOVASCULARIZATION; PROMOTES ANGIOGENESIS; EXTRACELLULAR-MATRIX;
D O I
10.3390/cells8080925
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Dysregulation of vascular networks is characteristic of eye diseases associated with retinal cell degeneration and visual loss. Visual impairment is also the consequence of photoreceptor degeneration in inherited eye diseases with a major inflammatory component, but without angiogenic profile. Among the pathways with high impact on vascular/degenerative diseases of the eye, a central role is played by a system formed by the ligand urokinase-type plasminogen activator (uPA) and its receptor uPAR. The uPAR system, although extensively investigated in tumors, still remains a key issue in vascular diseases of the eye and even less studied in inherited retinal pathologies such as retinitis pigmantosa (RP). Its spectrum of action has been extended far beyond a classical pro-angiogenic function and has emerged as a central actor in inflammation. Preclinical studies in more prevalent eye diseases characterized by neovascular formation, as in retinopathy of prematurity, wet macular degeneration and rubeosis iridis or vasopermeability excess as in diabetic retinopathy, suggest a critical role of increased uPAR signaling indicating the potentiality of its modulation to counteract neovessel formation and microvascular dysfunction. The additional observation that the uPAR system plays a major role in RP by limiting the inflammatory cascade triggered by rod degeneration rises further questions about its role in the diseased eye.
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页数:28
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