April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Further implication of Pigment Epithelium-Derived Factor (PEDF) in CAR
Author Affiliations & Notes
  • Charles E Thirkill
    Ocular Immunology, UC Davis, Davis, CA
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    Commercial Relationships Charles Thirkill, None
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Investigative Ophthalmology & Visual Science April 2014, Vol.55, 69. doi:
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      Charles E Thirkill, ; Further implication of Pigment Epithelium-Derived Factor (PEDF) in CAR. Invest. Ophthalmol. Vis. Sci. 2014;55(13):69.

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

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Abstract

Purpose: Preliminary studies of abnormal anti-retina antibody activity in the vision loss of patients with gynecological cancers led to the finding of an immunologic commonality involving a 45 kd protein antigen expressed within the outer segments of the retina and the cytoplasm of RPE cells. Continuing investigations sought to confirm these earlier findings, and determine if similar abnormal antibody activity could be found in other forms of cancer in which immune-mediated vision loss is suspected.

Methods: Western blot reactions on extracts of pig retina and in vitro cultivated retinal pigment epithelium were applied to identify CAR patients presenting with antibody activity within the region of 45 kd of extracts of both tissues. Indirect immunohistochemistry on 6 micron sections of rhesus monkey eyes were used to determine the location of the abnormal antibody within the neurosensory retina, and RPE cells.

Results: Three CAR patients, one with vision loss developing in association with colon cancer, another with lung cancer and another with renal carcinoma were identified by Western blot analyses on both retina and RPE to be reacting with abnormal antibody intensity within the region of 45 kd of blots of both tissues. Indirect immunohistochemistry identified each patient's antibody activity to be localized within the outer segments of the photoreceptor layer of the retina, and the cytoplasm of RPE cells.

Conclusions: Cancer patients experiencing an associated loss of vision may in some cases be found to be abnormally immunologically hyperactive with a 45 kd antigen which preliminary studies identified as the Pigment Epithelium-Derived Factor. When present, abnormal antibody activity with this ubiquitous and multifunctional protein is easily demonstrated within blots of retina and RPE. The consequences of this abnormality might result in an inhibition of the homeostatic influence of PEDF which includes control of the activity of Vascular Endothelial Growth Factor (VEGF). Any immune-mediated interference could allow VEGF to overact, encouraging unwanted vascular proliferations capable of providing growth encouraging nourishment to solid cancers. Findings made in these continuing studies serve to further implicate PEDF as a possible autoantigen involved in different forms of CAR in addition to that seen in gynecological cancers; an abnormality proposed here as an example of a novel ocular paraneoplasia; the 45 kd CAR syndrome.

Keywords: 432 autoimmune disease • 441 CAR • 554 immunohistochemistry  
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