NEUROTROPHIN-3 IS INCREASED IN SKIN IN HUMAN DIABETIC NEUROPATHY

Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been s hown to be necessary for the development of muscle spindle and Merkel cell affrerent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres termi nate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of end ogenous NT-3 in skin of 24 patients at different stages of diabetic po lyneuropathy have been investigated. NT-3 concentrations, measured wit h a specific immunoassay, were significantly higher in affected skin b iopsies from patients with diabetic neuropathy than matched control sk in (diabetic skin 6.32 (1.18) pg/mg upsilon control skin 1.28 (0.05) ( mean (SEM)); p < 0.004, Mann-Whitney U test), particularly in the late r stages. The optical density of NT-3-immunostaining was also signific antly greater in the epidermis in diabetic patients (diabetic epidermi s 0.30 (0.06) upsilon controls 0.24 (0.01); p < 0.02). No correlation was found between individual quantitative sensory tests and the increa se of NT-3 concentration. The increase of NT-3 seems to reflect the de gree of skin denervation in diabetic neuropathy, and may represent a c ompensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.