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

Proliferative Diabetic Retinopathy Clinical Trial

Official title:

Vitreous Levels of Patients With Proliferative Diabetic Retinopathy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00728598
• Other study ID #: 9561702008
• Status: Completed
• Phase: N/A
• First received: August 1, 2008
• Last updated: August 5, 2008
• Start date: January 1998
• Est. completion date: December 1998

Study information

• Verified date: August 2008
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 1998
• Est. primary completion date: December 1998
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Angiogenesis
• Diabetic Retinopathy
• Proliferative Diabetic Retinopathy
• Retinal Diseases

Locations

Country	Name	City	State
Taiwan	The department of ophthalmology, National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (2)

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. — View Citation

Petrovic MG, Korosec P, Kosnik M, Hawlina M. Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2007 Jan;143(1):175-6. Epub 2006 Sep 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vitreous levels and serum levels of Fractalkine, VEGF, other growth factor.		vitreous sample collected on vitrectomy	Yes