Melanoma Associated Retinopathy (MAR) is a paraneoplastic visual syndrome associated with cutaneous malignant melanoma in which patients typically experience a sudden decrease in night vision and sensations of shimmering lights. Electroretinogram (ERG) recordings from MAR patients are characterized by a "negative" waveform in which the a-wave, arising from photoreceptor transduction, is normal, but the b-wave, arising primarily from ON-bipolar cell activation, is absent or reduced. Significantly, serum from MAR patients has been shown to label retinal bipolar cells. The proposed research tests the hypothesis that autoantibodies in MAR patient serum are generated against proteins expressed in metastatic malignant melanocytes, but then target a protein complex functional in bipolar cells.
The aims of the research are to identify the retinal antigens in MAR, to elucidate the role of these proteins in normal bipolar cell physiology, and determine how these functions are perturbed in MAR.
The aims will be addressed with a multidisciplinary approach combining immunohistochemistry, cell biology, biochemistry, and electrophysiology. The results will generate new insights into cellular processes fundamental to vision and will contribute to our understanding of the link between cancer and autoimmune retinopathy.

Public Health Relevance

The proposed research will provide new insights into fundamental visual processes in the normal retina, and reveal how they are altered in autoimmune retinopathy. Identification of the retinal antigens in melanoma associated retinopathy will have applications in the clinic in the treatment of patients at risk for cancer associated autoimmune visual disease and in early diagnosis of tumor metastasis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY022369-01A1
Application #
8504164
Study Section
Special Emphasis Panel (DPVS)
Program Officer
Greenwell, Thomas
Project Start
2013-04-01
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$471,865
Indirect Cost
$165,459
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239