Effect of lysophosphatidylcholine acyltransferase-1 deficiency on the murine retinal structure and electroretinograms

Abstract

Objective To observe the effect of lysophosphatidylcholine acyltransferase-1 (LPCAT1)deficiency on the structure and electrophysiology of the murine retina.Methods Rd11 mice (Lpcat1 homozygous mutant,n =60) and wild-type C57BL/6J mice (n =60) were used in this study.Immunohistochemistry was performed to determine the expression of LPCAT1 in the mouse retina.Retinas of rd11 mice and age-matched control mice at postnatal 3,6,9-day and 2,4,6,8-week were paraffin embedded,sectioned and hematoxylin eosin stained,and full-field electroretinograms (F-ERG) were also recorded at these time points.Statistics were based on independent samples t-test.Results LPCAT1 was absent in rd11 mice retina.In wild-type C57BL/6J mice retina,LPCAT1 was expressed most strongly in the inner segment of photoreceptor cells,weak in the ganglion cell layer.Rd11 mouse exhibited retinal degeneration and eventual photoreceptor cell loss.Retinas of rd11 mice showed nearly half of the photoreceptor cells missing around postnatal week 4,and by 6-week after birth only two layers of nuclei remained.At postnatal week 8,nearly all photoreceptor cells were lost.Dark-adapted F-ERG showed reduced rod-driven response at 2 and 4 weeks of age,which was flattened by 6 and 8 weeks of age.By 2 weeks of age,no significant difference was found in b-wave amplitude between rd11 eyes [(72.8±15.6) μV]and C57BL/6J eyes [(105.2±21.1) μV] (t=-2.760,P=0.025).Compared with age-matched control mice [(231.8±32.0)μV],rod response of rd11 mice [(20.6±6.4) μV] decreased obviously at postnatal week4 (t=-14.471,P=0.000).Cone response was nearly normal at 2 and 4 weeks of age but substantially reduced at 6 weeks of age,which was flattened by 8 weeks of age.At 2 and 4 weeks after birth,no significant difference was found in b-wave amplitude between rd11 eyes [(46.8 ± 7.2),(78.0 ±8.2) μV] and C57BL/6J eyes [(42.8±6.4),(91.4±9.4) μV] (t=0.930,-2.401; P=0.379,0.043).Compared with age-matched control mice [(116.2 ± 12.9) μV],cone response of rd11 mice [(17.2 ± 2.0) μV]decreased obviously at postnatal week 6 (t =-17.008,P =0.000).Conclusion The layers of photoreceptor cells nuclei in rd11 mice decreases with age,and its F-ERG reflection is unusual. Key words: Lecithin acyltransferase deficiency; Retinal degeneration/pathology; Electroretinography