Fractalkine, a CX3C Chemokine, Act as a Mediator of Ocular Angiogenesis
Keywords
Abstract
Description
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.
Dates
Last Verified: | 07/31/2008 |
First Submitted: | 07/31/2008 |
Estimated Enrollment Submitted: | 08/04/2008 |
First Posted: | 08/05/2008 |
Last Update Submitted: | 08/04/2008 |
Last Update Posted: | 08/05/2008 |
Actual Study Start Date: | 12/31/1997 |
Estimated Primary Completion Date: | 11/30/1998 |
Estimated Study Completion Date: | 11/30/1998 |
Condition or disease
Phase
Arm Groups
Arm | Intervention/treatment |
---|---|
1 Proliferative diabetic retinopathy, active. | |
2 Proliferative diabetic retinopathy, quiescent. | |
3 Control group. Patients with macular hole or idiopathic epiretinal membrane receiving vitrectomy for their disease. |
Eligibility Criteria
Sexes Eligible for Study | All |
Sampling method | Non-Probability Sample |
Accepts Healthy Volunteers | Yes |
Criteria | 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. |
Outcome
Primary Outcome Measures
1. Vitreous levels and serum levels of Fractalkine, VEGF, other growth factor. [vitreous sample collected on vitrectomy]