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Abstract #47112 Published in IGR 13-3

Activation of autophagy in a rat model of retinal ischemia following high intraocular pressure

Piras A; Gianetto D; Conte D; Bosone A; Vercelli A
PLoS ONE 2011; 6: 22514

See also comment(s) by Natik Piri


Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21(plus or minus)1.13 vs controls 19.23(plus or minus)1.12 cells/500 (mu)m); this decrease was partially prevented by 3-methyladenine (17.08(plus or minus)1.42 cells/500 (mu)m), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia.

A. Piras. Neuroscience Institute of the Cavalieri Ottolenghi Foundation, Orbassano, Torino, Italy.


Classification:

5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)



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