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Rie Suzuki, Takayuki Oka, Yoshiyuki Tamada, Thomas R. Shearer, Mitsuyoshi Azuma; Involvement Of Calpain In The Degeneration And Dysfunction Of Rat Retinal Nerve Fiber Layers Due To Acute Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5372.
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Increased intraocular pressure (IOP) in human glaucoma leads primarily to damage of the retinal ganglion cell layer (GCL). Electrophysiological studies also suggest impairment of the inner plexiform layer and inner nuclear layer (IPL+INL). But damage to the photoreceptors (PR) is controversial. Our recent studies with acute ocular hypertensive rats confirmed damage predominantly in the GCL and IPL+INL, and only partial damage to the PR. Calpain-induced proteolysis was also observed in whole retina, and calpain inhibitor SNJ-1945 ameliorated degeneration of the GCL. However, involvement of calpain in damage to other nerve fiber layers was not clear. Thus, the purpose of present study was to determine where calpain causes degeneration and dysfunction in specific nerve fiber layers.
IOP in rats was elevated to 110 mm Hg for 40 min. Oral calpain inhibitor SNJ-1945 was administrated at 50 mg/kg 1 hour after ocular hypertension. Retinal function was assessed by scotopic electroretinography (ERG). Histologic damage was evaluated in thin sections of retina after H&E and immunostaining.
One day after ocular hypertension, the ERG b-wave, arising primarily from the on-bipolar cells, was lost and only minimally returned by day 7. The thickness of the IPL+INL containing these bipolar cells became thinner. Calpain protease inhibitor SNJ-1945 significantly ameliorated the loss of the b-wave as well as the thinning of IPL+INL at 7 days. Interestingly, the changes in amplitude of the b-wave were significantly correlated to changes in the thickness of IPL+INL. In contrast, elevated IOP caused only mild losses in the a-wave arising from the PR, the thickness of the OPL+OS containing the PR did not change, but SNJ-1945 did significantly ameliorate IOP-induced losses of the a-wave.
Elevated IOP in rats predominantly damaged the IPL+INL. Amelioration by the oral calpain inhibitor SNJ-1945 implicated calpain hydrolysis in the degeneration of bipolar cells. Although much less obvious, calpain activation may also damage PR cells.
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