Effect of lysophosphatidylcholine acyltransferase-1 deficiency on the murine retinal structure and electroretinograms_Chinese Journal of Ocular Fundus Diseases

Authors：

HanJuanjuan ,  DaiXufeng , ZhangHua , 戚艳 , 庞继景

School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou 325027, China;

Corresponding author：

DaiXufeng, Email: daixufeng@sohu.com

Keywords：

Lecithin acyltransferase deficiency; Retinal degeneration/pathology; Electroretinography

DOI：

10.3760/cma.j.issn.1005-1015.2014.03.015

Video：

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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 week 4 (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.

Citation： HanJuanjuan, DaiXufeng, ZhangHua. Effect of lysophosphatidylcholine acyltransferase-1 deficiency on the murine retinal structure and electroretinograms. Chinese Journal of Ocular Fundus Diseases, 2014, 30(3): 289-293. doi: 10.3760/cma.j.issn.1005-1015.2014.03.015 Copy

1.	Chen X, Hyatt BA, Mucenski ML, et al. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar typeⅡcells[J]. Proc Natl Acad Sci USA, 2006, 103:11724-11729.
2.	Mansilla F, da Costa KA, Wang S, et al. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer[J]. J Mol Med (Berl),2009,87:85-97.
3.	Friedman JS, Chang B, Krauth DS, et al. Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice[J]. Proc Natl Acad Sci USA, 2010,107:15523-15528.
4.	Chang B, Hawes NL, Hurd RE, et al. Mouse models of ocular diseases[J]. Vis Neurosci,2005,22:587-593.
5.	Xu Y, Saegusa C, Schehr A, et al. C/EBPalpha is required for pulmonary cytoprotection during hyperoxia[J]. Am J Physiol Lung Cell Mol Physiol,2009,297:286-298.
6.	Harayama T, Shindou H, Shimizu T. Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1[J]. J Lipid Res,2009,50:1824-1831.
7.	Bridges JP, Ikegami M, Brilli LL, et al. LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice[J]. J Clin Invest,2010,120:1736-1748.
8.	Zhou X, Lawrence TJ, He Z, et al. The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer[J]. Exp Mol Pathol,2012,92:105-110.
9.	Wu M, Tu T, Huang Y, et al. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene[J]. BMC Cancer,2013,13:44.
10.	Morita Y, Sakaguchi T, Ikegami K, et al. Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression[J]. J Hepatol,2013,59:292-299.
11.	Deng WT, Dinculescu A, Li Q, et al. Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats[J]. Invest Ophthalmol Vis Sci,2012, 53:1895-1904.
12.	Nakanishi H, Shindou H, Hishikawa D, et al. Cloning and characterization of mouse lung-type acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1): expression in alveolar typeⅡcells and possible involvement in surfactant production[J]. J Biol Chem, 2006, 281:20140-20147.
13.	Cheng L, Han X, Shi Y. A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice[J]. Am J Physiol Endocrinol Metab,2009,297:1276-1282.
14.	Wilson-Ashworth HA, Judd AM, Law RM, et al. Formation of transient non-protein calcium pores by lysophospholipids in S49 Lymphoma cells[J]. J Membr Biol,2004,200:25-33.
15.	Sharma AK, Rohrer B. Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line[J]. J Biol Chem,2004,279:35564-35572.
16.	Granit R. The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve[J]. J Physiol,1933,77: 207-239.
17.	Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa[J]. Lancet,2006,368:1795-1809.

1. Chen X, Hyatt BA, Mucenski ML, et al. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar typeⅡcells[J]. Proc Natl Acad Sci USA, 2006, 103:11724-11729.
2. Mansilla F, da Costa KA, Wang S, et al. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer[J]. J Mol Med (Berl),2009,87:85-97.
3. Friedman JS, Chang B, Krauth DS, et al. Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice[J]. Proc Natl Acad Sci USA, 2010,107:15523-15528.
4. Chang B, Hawes NL, Hurd RE, et al. Mouse models of ocular diseases[J]. Vis Neurosci,2005,22:587-593.
5. Xu Y, Saegusa C, Schehr A, et al. C/EBPalpha is required for pulmonary cytoprotection during hyperoxia[J]. Am J Physiol Lung Cell Mol Physiol,2009,297:286-298.
6. Harayama T, Shindou H, Shimizu T. Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1[J]. J Lipid Res,2009,50:1824-1831.
7. Bridges JP, Ikegami M, Brilli LL, et al. LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice[J]. J Clin Invest,2010,120:1736-1748.
8. Zhou X, Lawrence TJ, He Z, et al. The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer[J]. Exp Mol Pathol,2012,92:105-110.
9. Wu M, Tu T, Huang Y, et al. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene[J]. BMC Cancer,2013,13:44.
10. Morita Y, Sakaguchi T, Ikegami K, et al. Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression[J]. J Hepatol,2013,59:292-299.
11. Deng WT, Dinculescu A, Li Q, et al. Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats[J]. Invest Ophthalmol Vis Sci,2012, 53:1895-1904.
12. Nakanishi H, Shindou H, Hishikawa D, et al. Cloning and characterization of mouse lung-type acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1): expression in alveolar typeⅡcells and possible involvement in surfactant production[J]. J Biol Chem, 2006, 281:20140-20147.
13. Cheng L, Han X, Shi Y. A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice[J]. Am J Physiol Endocrinol Metab,2009,297:1276-1282.
14. Wilson-Ashworth HA, Judd AM, Law RM, et al. Formation of transient non-protein calcium pores by lysophospholipids in S49 Lymphoma cells[J]. J Membr Biol,2004,200:25-33.
15. Sharma AK, Rohrer B. Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line[J]. J Biol Chem,2004,279:35564-35572.
16. Granit R. The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve[J]. J Physiol,1933,77: 207-239.
17. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa[J]. Lancet,2006,368:1795-1809.

Chinese Journal of Ocular Fundus Diseases

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

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