BDNF attenuates retinal cell death caused by chemically induced hypoxia in rats.
OBJECTIVE
To investigate the neuroprotective effects of brain-derived neurotrophic factor (BDNF) against potassium cyanide (KCN)-induced retinal damage.


METHODS
Rats were injected intravitreally with iodinated BDNF. Two days later, eyeballs were dissected into various parts, and the level of radioactivity in each part was measured. Retinal damage was induced by incubating rat eyeballs with 5 mM KCN. BDNF was injected intravitreally 2 days before KCN treatment, and subsequent morphometric analysis was carried out to evaluate the retinal cell damage. To elucidate the mechanisms of BDNF's neuroprotective effects, the intravitreal concentrations of amino acids and the expression of calretinin were investigated.


RESULTS
Intravitreally injected BDNF was distributed evenly throughout the eyes, and the incorporation of iodinated BDNF into the retina was three times higher than in other ocular tissues. Immunohistochemical analysis demonstrated that exogenous BDNF diffused throughout the retina and was especially concentrated in the inner (INL) and outer nuclear layer. Morphometric analysis showed that the number of INL cells of the posterior area, 880 microm from the optic nerve head, was 190 +/- 4 with KCN treatment and 284 +/- 9 in control animals. Cell death appeared to be necrotic. When eyes injected with either phosphate-buffered saline (PBS) or BDNF were subjected to treatment with KCN, the number of INL cells was 186 +/- 5 in the PBS-treated controls and 253 +/- 8 in eyes treated with BDNF. Also, BDNF increased the number of calretinin-positive cells in the INL and reduced the KCN-induced elevation of intravitreal glutamate levels.


CONCLUSIONS
BDNF injected intravitreally reaches the retina and attenuates the INL cell death caused by KCN-induced metabolic insult. The neuroprotective effects of BDNF are partly ascribed to the upregulation of a calcium-binding protein and the attenuation of glutamate release into the vitreous body.
Ikeda
K
K
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Tanihara
H
H
Honda
Y
Y
Tatsuno
T
T
Noguchi
H
H
Nakayama
C
C
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D064032:Calbindin 2; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D005136:Eye Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D011190:Potassium Cyanide; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C576512:Calb2 protein, rat; D064032:Calbindin 2; D005136:Eye Proteins; D018696:Neuroprotective Agents; D064030:S100 Calcium Binding Protein G; D018698:Glutamic Acid; D011190:Potassium Cyanide