advertisement

Editors Selection IGR 13-3

Basic Research - RGC: Calpain causes hypoxic damage of retinal cells

Comment by Rebecca Sappington on:

46428 Calpain, not caspase, is the causative protease for hypoxic damage in cultured monkey retinal cells, Nakajima E; Hammond KB; Rosales JL et al., Investigative Ophthalmology and Visual Science, 2011; 52: 7059-7067

Find related abstracts

Ischemia-reperfusion injury is a pathogenic factor in several retinal degenerations, including age-related macular degeneration, diabetic retinopathy and possibly, glaucoma. Although the relationship between ischemia/reperfusion and cell death is clear, the mechanisms leading to cell death are not well understood. In apoptosis induced by ischemia-relevant stressors, activation of calpains and caspase-3 is responsible for proteolysis of a variety of substrates, including cytoskeletal proteins and poly (ADP-ribose) polymerase. Nakajima et al. (1168) sought to elucidate the role of calpains and caspase-3 in hypoxia/reoxygenation-induced apoptosis of photoreceptor and M&uum;ller cells from non-human primate retina. In their study, Nakajima et al. exposed primary cultures of mixed retinal cells from rhesus monkeys to 1-2 days of hypoxic conditions followed by 0-1 day of normoxia in the presence or absence of calpain inhibitor (SNJ-195) or caspase-3 inhibitor (z-VAD-fmk). Outcome measures included TUNEL reactivity, morphological analyses and analysis of proteolytic and autolytic activity for calpains and caspase-3 (pro-caspase-3, α-spectrin, rhodopsin, m-opsin, vimentin, casein) by immunoblotting and zymography. The primary finding was that inhibition of calpains, but not caspase-3, reduced TUNEL-reactivity and proteolysis of α-spectrin and photoceptor and Müller cell markers induced by hypoxia/reoxygenation. The study also provided some evidence for caspase-3 proteolysis by calpains, but only in the presence of exogenous pro-caspase 3. Like most studies utilizing mixed retinal cultures, the most pronounced weakness of this study is cell-type specificity. Photoreceptors and Müller cells were identified immunohistochemically; however, the study acknowledges that bipolar cells were also present. In addition, there is no mention of microglia or astrocytes, the latter of which can express vimentin, the marker used to identify Müller cells, under pathological conditions. Despite these issues, the immunoblotting and, to a lesser extent, the zymography data warrant further investigation of calpain-mediated apoptosis in specific cell types following ischemia/reperfusion injury in the primate retina.

• ← Previous
• Next →