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Maki Kayama, Toru Nakazawa, Yusuke Murakami, Yuki Morizane, Aristomenis Thanos, Demetrios Vavvas, Joan W. Miller; Inhibition Of Heat Shock Protein 70 Can Prevent Muller Glial Proliferation After Retinal Detachment?. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5469.
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© ARVO (1962-2015); The Authors (2016-present)
After retinal detachment (RD), Muller glia quickly proliferates and fills space left by dying photoreceptor cells. It inflicts scar formation in retina and subsequently affects retinal architecture. We hypothesized the inhibition of Muller glial proliferation can prevent this sequential process. Heat Shock Proteins (HSPs) are known to prevent protein aggregation and facilitate refolding of dysfunctional proteins, important to the survival of all organisms. Here, we investigated whether inhibition of HSP70 could prevent Muller glial proliferation after RD in rats.
RD was induced in adult rats by subretinal injection of sodium hyaluronate. One hour before RD induction, 250ul of an HSP70 inhibitor (quercetin, 100mg/ml, n=6) or dimethyl sulfoxide was injected intraperitoneally. In addition, 250ul of an HSP70 inducer (Geranylgeranylacetone, gift from Eisai Co., Ltd, 200mg/ml, n=6) or phosphorylated buffer solution (PBS, n=6) were intraperitoneally injected daily starting at 2 days prior to and up to 3 days after RD induction. Animals were sacrificed 1, 3 or 7 days after RD. Activation of Muller glia was quantified by GFAP. Phosphorylated extracellular signal-regulated kinase (Erk) activation was evaluated by immunoblotting and immunohistochemistry.
At 1, 3 and 7 days after RD, the expression of GFAP was up-regulated in the PBS group time dependent manner (3.8, 4.9, ¬7.4-fold respectively). At day 1, treatment with HSP70 inhibitor inhibited GFAP expression level (0.65-fold), phosphorylated Erk1 (0.63-fold) and Erk2 (0.85-fold) compared with PBS group (p<0.05). On the other hand, treatment with HSP70 inducer increased GFAP expression level (1.72-fold) and accelerated phosphorylation of Erk1 (2.21-fold) and Erk2 (2.35-fold) compared with PBS group (p<0.05). Intensive GFAP and phosphorylation of Erk immunoreactivity were detected in Muller cell bodies and their processes by staining.
Inhibition of HSP70 attenuates Muller glia proliferation after RD and also suppresses phosphorylation of Erk. Inhibition of HSP70 may prevent change of retinal architecture associated with RD.
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