Elevated levels of calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy

Purpose: To detect the levels of the sensory peptide calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy and to compare them with those of uninflamed eyes (cataract and uncomplicated rhegmatogenous retinal detachment). Materials and methods: Using a highly specific and sensitive radioimmunoassay the concentration of calcitonin gene-related peptide was detected in fresh samples of aqueous humor obtained via paracentesis. Furthermore, calcitonin gene-related peptide-like immunoreactivities were characterized by high-pressure liquid chromatography. Results: The mean level of calcitonin gene-related peptide was 6.11 fmol/ml in cataract controls and 14.77 fmol/ml in uncomplicated rhegmatogenous retinal detachment. In the cataract group, 9 of 18 cases were below the detection limit and in the retinal detachment group, 5 of 16. In proliferative vitreoretinopathy, the peptide averaged 76.92 fmol/ml and none of the samples was below the detection limit. High-pressure liquid chromatography revealed one major peak corresponding to synthetic calcitonin gene-related peptide. Conclusion: In recent studies, we found elevated levels of the sensory peptide substance P in aqueous humor of patients with proliferative vitreoretinopathy. This fact and the present result, the elevation of calcitonin gene-related peptide in aqueous humor of eyes with proliferative vitreoretinopathy, clearly point to an involvement of sensory peptides in the pathobiology of the disease. The source of the elevation is not clear, but we hypothesize that it originates from a neurogenic mechanism, i.e. an acceleration of the peptides by their enhanced release from the iris/ciliary body complex subsequent to sensitization of sensory neurons, thus representing a very interesting epiphenomenon of proliferative vitreoretinopathy. Our results constitute novel aspects in the pathophysiological concept of proliferative vitreoretinopathy and extend the knowledge about the pathobiology of the disease process.