Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells.
Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P < 0.005) and 74% (P < 0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to one-half that of controls (P < 0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, Niigata 951-8585, Japan.
Masaaki
M
Seki
Takayuki
T
Tanaka
Hiroyuki
H
Nawa
Tomoaki
T
Usui
Takeo
T
Fukuchi
Kazuhito
K
Ikeda
Haruki
H
Abe
Nobuyuki
N
Takei
D025042:Amacrine Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology; D008297:Male; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D020933:Neurotrophin 3 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine