BDNF attenuates retinal cell death caused by chemically induced hypoxia inrats

PURPOSE. To investigate the neuroprotective effects of brain-derived neurot rophic factor (BDNF) against potassium cyanide (KCN)-induced retinal damage . METHODS. Rats were injected intravitreally with iodinated BDNF. Two days la ter, eyeballs were dissected into various parts, and the level of radioacti vity in each part was measured. Retinal damage was induced by incubating ra t eyeballs with 5 mM KCN. BDNF was injected intravitreally 2 days before KC N treatment, and subsequent morphometric analysis was carried out to evalua te the retinal cell damage. To elucidate the mechanisms of BDNF's neuroprot ective effects, the intravitreal concentrations of amino acids and the expr ession 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 ti mes higher than in other ocular tissues. Immunohistochemical analysis demon strated that exogenous BDNF diffused throughout the retina and was especial ly concentrated in the inner (INL) and outer nuclear layer. Morphometric an alysis showed that the number of INL cells of the posterior area, 880 mu m from the optic nerve head, was 190 +/- 4 with KCN treatment and 284 +/- 9 i n control animals. Cell death appeared to be necrotic. When eyes injected w ith either phosphate-buffered saline (PBS) or BDNF were subjected to treatm ent with KCN, the number of INL cells was 186 +/- 5 in the PBS-treated cont rols and 253 +/- 8 in eyes treated with BDNF. Also, BDNF increased the numb er of calretinin-positive cells in the INL and reduced the KCN-induced elev ation of intravitreal glutamate levels. CONCLUSIONS. BDNF injected intravitreally reaches the retina and attenuates the INL cell death caused by KCN-induced metabolic insult. The neuroprotec tive effects of BDNF are partly ascribed to the upregulation of a calcium-b inding protein and the attenuation of glutamate release into the vitreous b ody.