First Author | Ha Y | Year | 2011 |
Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
Issue | 10 | Pages | 7749-60 |
PubMed ID | 21862648 | Mgi Jnum | J:181592 |
Mgi Id | MGI:5312006 | Doi | 10.1167/iovs.11-8169 |
Citation | Ha Y, et al. (2011) Late-onset inner retinal dysfunction in mice lacking sigma receptor 1 (sigmaR1). Invest Ophthalmol Vis Sci 52(10):7749-60 |
abstractText | PURPOSE: Sigma receptor 1 (sigmaR1) is expressed abundantly in the eye, and several reports suggest that this putative molecular chaperone plays a role in lens cell survival, control of intraocular pressure (IOP), and retinal neuroprotection. The present study examined the consequence of the absence of sigmaR1 on ocular development, structure, and function. METHODS: Wild-type (sigmaR1/), heterozygous (sigmaR1/), and homozygous (sigmaR1/, knockout) mice aged 5 to 59 weeks were subjected to comprehensive electrophysiological testing and IOP measurement. The eyes were examined by light and electron microscopy and subjected to morphometric examination and detection of apoptosis. RESULTS: Cornea and lens of sigmaR1/ mice were similar to wild-type mice in morphologic appearance at all ages examined, and IOP was within normal limits. Comprehensive ERG and morphometric analyses initially yielded normal findings in the sigmaR1/ mice compared with those in the wild-type. By 12 months, however, significantly decreased ERG b-wave amplitudes and diminished negative scotopic threshold responses, consistent with inner retinal dysfunction, were detected in sigmaR1/ mice. Concomitant with these late-onset changes were increased TUNEL- and active caspase 3-positive cells in the inner retina and significant loss of cells in the ganglion cell layer, particularly in the central retina. Before these functional and structural abnormalities, there was ultrastructural evidence of axonal disruption in the optic nerve head of sigmaR1/ mice as early as 6 months of age, although there were no alterations observed in retinal vascularization in sigmaR1/ mice. CONCLUSIONS: These data suggest that lack of sigmaR1 leads to development of late-onset retinal dysfunction with similarities to optic neuropathy. |