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T. Seki, M. Nakatani, Y. Shinohara, C. Taki, M. Ozawa, S. Nishimura, S. Shioda; Protective Effect of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) on Kainic Acid – Induced Neurotoxicity in the Rat Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):164.
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Purpose: To determine if pituitary adenylate cyclase–activating polypeptide (PACAP) has any neuroprotective effects against kainic–acid (KA)–induced retinal damage. Methods: In adult Wistar rats, either PACAP 38 (10 pmol) or saline only was injected into the vitreous body 2 days before or concurrently with KA (5 nmol) injection. In another group, 100 nmol of 6–cyano–7–nitroquinoxaline–2,3–dione (CNQX), a non–N–methyl–D–aspartate receptor antagonist, was co–injected with KA as a positive control . KA–induced neuronal damage was evaluated at 7 days after KA injection by determining phosphorylated neurofilament heavy chain subunit (pNF–H) contents in the retina and optic nerve (ON) extract by the enzyme–linked immunosorbent assay (ELISA) system we previously reported. Expression and localization of interleukin–6 (IL–6) in the retinal cross–section was assessed by immunohistochemistry at 6 hours, 1, 2, 3 and 7 days after PACAP 38 (10 pmol) treatment. Results: Pre–treatment with PACAP 38 significantly inhibited the loss of pNF–H content in the retina compared to the saline–treated control (p < 0.01). However, PACAP 38 co–injected with KA caused no significant changes in either retina or ON, while CNQX treatment almost completely inhibited KA–induced damages. In the immunohistochemical study for IL–6, positive radial stainings throughout the retina (presumably Muller cells) were observed as early as 2 days after treatment, and maximum immunoreactivities were observed at 2 and 3 days after PACAP 38 treatment. Conclusions: Exogeneous PACAP 38 is likely to protect inner retinal cells from KA–induced neuronal damage, and its protective effect may involve IL–6 expression in Muller cells.
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