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Protective Effects of PF-4708671 Against N-methyl-d-aspartic Acid-Induced Retinal Damage in Rats

Protective Effects of PF-4708671 Against N-methyl-d-aspartic Acid-Induced Retinal Damage in Rats

Ikumi Hayashi, Yuto Aoki, Hiroko Ushikubo, Daiki Asano, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii

Fundam Clin Pharmacol. 2016 Dec;30(6):529-536.

PMID: 27371338

Abstract:

We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1255517760	PF-4708671		1255517-76-0	Price

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