Elevated neprilysin activity in vitreous of patients with proliferative diabetic retinopathy.
OBJECTIVE
Diabetic retinopathy (DR) is the leading cause of blindness in the industrialized world. Hyperglycemia induces retinal hypoxia, which upregulates a range of vasoactive factors that may lead to macular edema and/or angiogenesis, and hence potentially to sight-threatening retinopathy. The control of signal-peptide activity by cell-surface proteases is one of the main factors regulating the development and behavior of organisms. In mammals, neprilysin is known to play a key role in these processes, and its inactivation can initiate cellular disorganization. Neprilysin is a rate-limiting peptidase involved in the physiological degradation of amyloid beta (Abeta) in the brain. In this study, we measured both the enzymatic activity of neprilysin and the concentration of Abeta in patients with proliferative DR (as compared to their levels in patients with macular hole), and we analyzed their association.


METHODS
In vitreous samples collected from patients who underwent vitrectomy, an HPLC-fluorometric system (recently established by us), and sensitive and specific enzyme-linked immunosorbent assays were used to determine the enzymatic activity of neprilysin and the concentration of Abeta.


RESULTS
By comparison with the levels in the control (macular-hole) patients, there was a significant increase in neprilysin activity level and a significant decrease in Abeta level in proliferative DR patients. There was a significant inverse correlation between neprilysin and Abeta among all subjects.


CONCLUSIONS
Neprilysin activity and Abeta concentrations displayed converse changes in patients with proliferative DR.
Hara
Hideaki
H
Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, Japan. hidehara@gifu-pu.ac.jp
Oh-hashi
Kentaro
K
Yoneda
Shinji
S
Shimazawa
Masamitsu
M
Inatani
Masaru
M
Tanihara
Hidenobu
H
Kiuchi
Kazutoshi
K
D016229:Amyloid beta-Peptides / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005470:Fluorometry; D006801:Humans; D015260:Neprilysin / Q000378:metabolism*; D009994:Osmolar Concentration; D012167:Retinal Perforations / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015260:Neprilysin