Ultrastructural characterization and histopathology of melanoma associated autoimmune retinopathy

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NEI	IMMUNO-2

Authors

• MS Abu-Asab
• Y Wang
• W Li
• C-C Chan

Abstract

Melanoma-associated retinopathy (MAR) results from the cross-reaction of tumor-directed autoantibodies with retinal antigens. We present for the first time ocular ultrastructure and autoantibodies of MAR. The autopsied eyes of a metastatic cutaneous melanoma patient and positive retinal autoantibodies were examined with histopathology including transmission electron microscopy, and immunohistochemistry (Calbindin, PKC-alpha, and TRPM1). The outer plexiform layer (OPL) was the most affected retinal tissue in both eyes; it showed thinning and atrophy, which extended to both the outer and inner nuclear layers (ONL & INL), resulting in focal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Ultrastructural damages within OPL included extensive homogenous deterioration of the synapses characterized by numerous empty vacuoles, disintegrated mitochondria, disorganization and stacking of filaments, and numerous apoptotic bodies. OPL bordering cells in the INL and ONL showed cytoplasmic deterioration. Aberrant immuno-reactivities illustrated blurred condensed bipolar dendritic structure (TRPM1), tightly packed INL (PKC), and loss of ONL (calbindin), which suggested abnormal TRPM1 cation channels of retinal ON bipolar cells. This study provided the first structural evidence that MAR-autoantibodies target channels in the dendritic terminals of ON bipolar cells and produce abnormal synaptic transmission; these are possibly the main mechanism for MAR retinopathy.

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