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M. Ohashi, S. Saito, Y.–N. Chen, M. Aihara, M. Araie; Bax–Inhibiting Peptides Prevents Glutamate–Induced Neurotoxicity in Rat Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4841.
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© ARVO (1962-2015); The Authors (2016-present)
Bax–inhibiting peptide (BIP) is a membrane permeable peptide comprised of five amino acids (VPMLK) designed from the Bax–binding domain of Ku70. It inhibits Bax–mediated translocation of cytochrome c and suppresses mitochondria–dependent apoptosis. We have evaluated the neuroprotective effects of BIP against glutamate receptors–mediated retinal damage in rat.
[in vivo] NMDA (N–methyl–D–aspartic acid 200nmol) or KA(kainate acid 3nmol) was injected to vitreous of Male Sprague–Dawley rats to induce excitotoxic retinal ganglion cells (RGCs) damage. VPMLK(12nmol) was injected with NMDA or KA intravitreously. The extent of RGC damage was evaluated by histological measurement of inner retinal cell layer thickness and by RGC counting with retrograde DiI labeling of RGCs 7 days after the injection. [in vitro] Purified RGCs were obtained from retina of 6–to 7–day–old rats utilizing the two–step immno–panning procedure and cultured in serum–free medium. After being pre–incubated with VPMLK (10, 50 and 200 µM) for 2 hrs, excitotoxic agent agonists (NMDA 50µM or KA 25µM) were added to the RGCs. Then the RGCs were incubated for 72 hours. Using the calcein–AM assay, the numbers of the viable cells were counted and the cell viability percentages were calculated compared with the control group, in which no excitotoxic agent agonists were added.
[in vivo] Intravitreal injection of NMDA or KA reduced thickness of the inner plexiform layer (IPL) to 53%,47% of control and reduced the number of RGCs to 65%,62% of control, respectively. Co–injection of VPMLK significantly prevented retinal damage (IPL:77%,81% RGC:80%,86% of control, respectively) . [in vitro] The viability percentage of RGC cultures with NMDA treatment was 73.3% without BIP treatment. The viability increased in a dose dependent manner with exposure to VPMLK (10µM:77.3%, 50µM:81.5%, 200µM:93.2%). On the other hand, the viability percentage of RGC cultures with KA treatment was 63.9% without BIP treatment. The viability also increased in a dose dependent manner with exposure to VPMLK (10µM: 70.8%, 50µM:80.4%, 200µM:83.9%).
BIP prevents glutamate–induced neurotoxicity in rat retina.
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