MECHANISM OF RETINAL DAMAGE IN AUTOIMMUNE RETINOPATHY

$47,603P51FY2010RRNIH

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer Associated Retinopathy (CAR) is a paraneoplastic disease in which retinal degeneration occurs as a result of the patient's immune response to cancer in a distal part of the body. Treatment for the primary malignancy does not alter the course of visual loss and there is neither a means of cure nor prevention of such retinal degenerations. Autoantibodies against retinal proteins are present in serum of CAR patients but whether these antibodies themselves induce retinal degeneration is a source of debate. Retinal dysfunction or degeneration is assessed by recording the electroretinogram (ERG). The ERG is a recording of the change in voltage across the retina in response to light and is recorded from an electrode placed against the cornea. The aim of the proposed studies was to use the ERG to assess changes in retinal function in rats following intravitreal injection autoantibodies isolated from CAR patients. The overall aim of the research is to determine the molecular mechanisms altered by autoantibodies against retinal proteins that lead to retinal degeneration. Understanding the molecular mechanisms that result in retinal degeneration in these patients is the first step towards the developing and testing of preventative treatments. Retinal function was not altered following intra-vitreal injection of antibodies against recoverin, alpha-enolase or carbonic anhydrase. Why these antibodies obtained from CAR patients did no alter the ERG remains unknown. Variation in epitope recognition, for example, between our patients may account for some of the variability in ERG results, and in patients. Another possibility is that a single injection of autoantibodies does not mimic the continuous exposure of the retina to these antibodies as occurs in CAR patients.

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