title: Imbalance of the nerve growth factor and its precursor as a potential biomarker for diabetic retinopathy.
abstract: Our previous studies have demonstrated that diabetes-induced oxidative stress alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation of its precursor, proNGF, at the expense of NGF which plays a critical role in preserving neuronal and retinal function. This imbalance coincided with retinal damage in experimental diabetes. Here we test the hypothesis that alteration of proNGF and NGF levels observed in retina and vitreous will be mirrored in serum of diabetic patients. Blood and vitreous samples were collected from patients (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University under approved IRB. Levels of proNGF, NGF, and p75(NTR) shedding were detected using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced proNGF expression and impaired NGF expression were observed in vitreous and serum. Vitreous and sera from diabetic patients (n = 11) showed significant 40.8-fold and 3.6-fold increases, respectively, compared to nondiabetics (n = 9). In contrast, vitreous and sera from diabetic patients showed significant 44% and 64% reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF ratios showed significant correlation between vitreous and serum. Further characterization of diabetes-induced imbalance in the proNGF to NGF ratio will facilitate its utility as an early biomarker for diabetic complications.
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: B A
authors: BA
authors: Mysona
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: S
authors: S
authors: Matragoon
authors: Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA.
authors: M
authors: M
authors: Stephens
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: I N
authors: IN
authors: Mohamed
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: A
authors: A
authors: Farooq
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: M L
authors: ML
authors: Bartasis
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: A Y
authors: AY
authors: Fouda
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: A Y
authors: AY
authors: Shanab
authors: Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA.
authors: D G
authors: DG
authors: Espinosa-Heidmann
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA ; Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA ; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, Augusta, USA.
authors: A B
authors: AB
authors: El-Remessy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism*; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood* / Q000378:metabolism*; D005260:Female; D005845:Georgia; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000097:blood* / Q000378:metabolism*; D010865:Pilot Projects; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C502240:NGF protein, human; D011498:Protein Precursors; D020932:Nerve Growth Factor