We thank Dr. Nakayama and Dr. Tamura for their interest in our recent contribution to Image of the Month1 and for allowing us to share their broad knowledge on copper, metallothionein, and porphyrin autofluorescence. Their elaborate spectroscopic and biochemical explanations are beyond our area of expertise, and we do not have direct experience with the Long-Evans cinnamon rat model of Wilson disease.
We made the simple histological observation that autofluorescent granules in human liver tissue from well-characterized patients with Wilson disease or chronic cholestasis stain with both orcein and rhodanine in keeping with a high content in sulfhydril groups and copper, respectively. The large size of the fluorescent granules suggested that we were not dealing with metallothionein-copper alone, but with a large amount of copper incorporated into the not entirely characterized lysosomal complex of metallothionein polymers with a glycoprotein component, as supported by periodic acid–Schiff staining. We realized that copper-metallothionein autofluorescence was well-known in earlier literature, and wondered about its possible practical use and the potential role of autofluorescence in liver pathology as quoted in an excellent review on the subject.2 We thought it was worth sharing this matter in the Image of the Month forum and remain glad to have generated some academic debate.