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Charles E. Thirkill; Immunological Inhibition of Pigment Epithelium-Derived Factor (PEDF) ?. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6241.
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The biological activity of Pigment Epithelium-Derived Factor (PEDF, molecular weight 45 kd) includes the inhibition of the activity of Vascular Endothelial Growth Factor (VEGF,molecular weight 45 kd with smaller isoforms). Both of these ubiquitous factors are multi-functional. Of relevance to this study is the recognized expression of PEDF and VEGF within the retinal pigment epithelium. The combination of these two factors normally contributes to the balance of activity that maintains ocular homeostasis. Any immunological inhibition of PEDF might result in an imbalance encouraging the blood vessel propagation typical of several diseases that involve uncontrolled vascular proliferation, such as that seen in some cancers, diabetic retinopathies and Age-Related Macular Degenerations. A search for evidence that might implicate the immunological inhibition of PEDF was performed on cancer patients presenting with evidence of the 45 kd CAR syndrome. Rationale: PEDF shares the same molecular mass as the unidentified 45 kd CAR antigen raising suspicion they might be one and the same molecule. The possibility of immunological inhibition of the activity of PDEF might then be of significance in both tumor growth, and its role in maintaining introcular equilibrium. The option that the 45 kd CAR antigen may be the 45 kd glycoprotein VEGF was included in these inquiries, but the potent antibody activity against this antigen did not support the likelihood.
Western blot analyses were performed on the patient’s antibody activity with the protein components of pig retina, and in vitro cultivated retinal pigment epithelium (ATCC ARPE-19 CRL-2302). The 45 kd component of retinal pigment epithelium was immunoprecipitated from an extract of cultured RPE using 45 kd reactive cancer patient’s serum, and the precipitate subjected to proteomic analysis.
Preliminary proteomic analyses implicate pigment epithelium-derived factor as the 45 kd antigen of interest.
The possibility of an antibody-mediated interferece in the biolocal activity of pigment epithelium-derived factor leads to a testable hypothesis: "Immunological inhibition of the modulating anti-vascular proliferation properties of pigment epithelium-derived factor results in a loss of homeostasis leading to the excessive production of blood vessels that typifies some forms of cancer, and retinopathies that involve uncontrolled vascular propagation". If this hypothesis proves correct it will introduce the prospect of ameliorating the pathological process of unwanted vascular spread through approriate targeted immunomodulation therapy.
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