Fractalkine, a CX3C Chemokine, Act as a Mediator of Ocular Angiogenesis

Study Overview
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Brief Summary
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Fractalkine (FKN) is a chemoattractant and adhesion molecule for leukocytes. Angiogenic effect of FKN also has been reported. We investigate FKN-mediated angiogenesis in ocular angiogenic disorders.

Detailed Description
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Fractalkine (FKN), the sole member of the CX3C chemokine family, is named for its fractal geometry. The CX3C motif, with three amino acids between the two terminal cysteines, makes fractalkine distinct from other chemokines.The structure of fractalkine, a membrane-bound glycoprotein with the chemokines domain atop an extended mucin-like stalk, also is unique.Membrane-bound FKN can be markedly induced on primary endothelial cells by inflammatory cytokines; this form promotes the robust adhesion of monocytes and T lymphocytes. Soluble FKN can be released by proteolysis at an efficient chemotactic activity level for monocytes and T cells. Thus, FKN is a versatile molecule regulating both cell-cell interactions in its membrane-bound form and directed-cell migration in its soluble form. The receptor of FKN, CXC3R1, is a G protein-couple protein, which expresses T lymphocytes, monocytes, natural killer (NK) cells, microglia, and neurons.Sulfation of tyrosine enhances the function of CX3CR1 in cell capture and firm adhesion. Fractalkine is expressed constitutively in the kidney, heart, lung, and brain. Fractalkine has demonstrated an important role in CNS inflammation, cardiac allograft rejection, arteriogenesis, renal disease, psoriasis, and during pregnancy. Silverman et al demonstrated the presence of FKN in normal cultured microvascular endothelial and stromal cells of iris and retina in vitro. Upon inflammatory cytokine stimulation, EC also express FKN and its receptors with FKN secretion in an autocrine manner. In addition to EC chemotaxis and tube formation, FKN is an angiogenic mediator in rheumatoid arthritis. Therefore, we hypothesize that FKN not only participates in ocular inflammatory reactions, but also plays an important role in ocular angiogenesis.

Official Title
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Vitreous Levels of Patients With Proliferative Diabetic Retinopathy.

Conditions
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Proliferative Diabetic Retinopathy, Angiogenesis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical diagnosis of proliferative diabetic retinopathy. who will receive vitrectomy for treatment of disease. Exclusion Criteria: previous ocular surgical history. history of uveitis history of ocular trauma.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Proliferative diabetic retinopathy, active. | |
| 2<br>Proliferative diabetic retinopathy, quiescent. | |
| 3<br>Control group. Patients with macular hole or idiopathic epiretinal membrane receiving vitrectomy for their disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitreous levels and serum levels of Fractalkine, VEGF, other growth factor. |  | vitreous sample collected on vitrectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proliferative diabetic retinopathy, Angiogenesis, Vitreous levels, Vascular endothelial growth factor, Fractalkine, Growth factor