September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Gynecological CAR, PEDF Hypersensitivity, and the HeLa Connection
Charles E. Thirkill Ph.D.
Ocular Immunology, Lab 1220 Surge III, 1263 Bioletti Way, U.C.Davis, CA. 95616.
Author Affiliations & Notes
  • Charles E Thirkill
    Ophthalmology and Vision Science, UC Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Charles Thirkill, None
  • Footnotes
    Support  Research to Prevent Blindness (RPB, and NEI core grant 1 P30 EY12576-08
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 498. doi:
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      Charles E Thirkill; Gynecological CAR, PEDF Hypersensitivity, and the HeLa Connection
      Charles E. Thirkill Ph.D.
      Ocular Immunology, Lab 1220 Surge III, 1263 Bioletti Way, U.C.Davis, CA. 95616.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):498.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The complexities of the pathogenesis of immune-mediated vision loss in cancer patients (Cancer-Associated Retinopathies; CAR), led to this continuing inquiry into the cause of the related immunologic abnormalities. The study focused on women with ovarian cancer who lost vision while exhibiting an unusual state of hypersensitivity with a 45 kDa antigen expressed in both retina and retinal pigment epithelium (RPE).

Methods : The antibody activity of three gynecological CAR patients experiencing rapid onset loss of vision was evaluated on Western blots of retina, RPE, HeLa cells (ATCC ARPE-19), and recombinant PEDF (Sigma SRP 4988). The recombinant antigen included due to previous findings implicating the 45 kDa antigen as the Pigment Epithelium-Derived Factor (PEDF). The HeLa cell line because of its origin in gynecological cancer.

Results : Each of the three gynecological CAR patients were producing antibodies reactive within the 45 kDa region of Western blots of retina and RPE. Equivalent antibody reactions were found on blots of HeLa cells and commercially obtained recombinant PEDF (Sigma). Findings were verified with mouse monoclonal anti-PEDF (Millipore MAB 1059).

Conclusions : The multifunctional nature of PEDF includes its control over the activity of the Vascular Endothelial Growth Factor (VEGF). Accordingly, consideration must be given to the possibility that anti-PEGF antibodies might inhibit its functions, depriving the host of its recognized anti-cancer activity, and its influence over excessive vascular spread resulting from a loss of control over VEGF. Immunologic inhibition of the actions of PEDF might then encourage malignant growth through a reduction in its natural anti-cancer activity, and lead to the cancer’s acquisition of a nurturing blood supply through the excessive activity of VEGF.
PEDF is expressed in the eye within the photoreceptor outer segments, and the RPE. The HeLa cell line is also known to express PEDF, as do several other malignancies. Any excessive production of PEDF by the patient’s cancer might result in an abnormal immune response to this influential protein. Anti-PEDF could explain the patient's loss of vision as a cancer-induced immune-mediated attack upon the retinal photoreceptor outer segments and the RPE, coupled with a loss of control over VEGF resulting in abnormal vascular spread.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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