Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.
The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5.
Phillips
M Joseph
MJ
University of Houston, College of Optometry, Houston, Texas 77204, USA.
Otteson
Deborah C
DC
Sherry
David M
DM
D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D015415:Biomarkers; D050598:Vesicular Glutamate Transport Protein 1; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse
Exp Eye Res. 2008 Apr;86(4):601-11
18294631
Prog Retin Eye Res. 2005 May;24(3):395-431
15708835
J Comp Neurol. 2003 Jan 1;455(1):1-10
12454992
J Comp Neurol. 2004 Sep 27;477(4):386-98
15329888
Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3449-56
18408183
J Rehabil Res Dev. 2006 Sep-Oct;43(6):723-32
17310421
Invest Ophthalmol Vis Sci. 2008 May;49(5):2148-55
18436848
J Clin Invest. 2004 Sep;114(6):765-74
15372100
J Comp Neurol. 1979 Sep 15;187(2):359-72
489784
Vision Res. 2007 Mar;47(5):624-33
17267005
J Neurosci. 1998 Sep 15;18(18):7336-50
9736654
Mol Vis. 2008 Apr 25;14:782-806
18483561
Science. 2000 Mar 17;287(5460):2032-6
10720333
Mol Neurobiol. 2003 Oct;28(2):139-47
14576452
Mol Vis. 2006 Dec 29;12:1706-14
17213800
Mol Ther. 2009 May;17(5):778-86
19293779
Exp Eye Res. 2005 Aug;81(2):123-37
15916760
J Neurosci Res. 2000 Aug 1;61(3):321-8
10900079
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13654-9
15353594
Prog Retin Eye Res. 2003 Sep;22(5):607-55
12892644
Eur J Neurosci. 2009 Apr;29(8):1533-42
19385989
Vision Res. 2003 Apr;43(8):867-77
12668056
Cloning Stem Cells. 2008 Sep;10(3):391-402
18729769
Adv Exp Med Biol. 2006;572:397-402
17249602
Cell Tissue Res. 2001 Aug;305(2):247-53
11545262
Nat Neurosci. 1999 Dec;2(12):1055-62
10570481
Neuroscience. 2008 Aug 26;155(3):698-713
18639614
J Comp Neurol. 2007 Jan 10;500(2):222-38
17111372
J Comp Neurol. 2009 Jun 10;514(5):473-91
19350664
Mol Cell Neurosci. 2008 Jul;38(3):341-8
18462949
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1488-93
9037080
Exp Eye Res. 2009 Jan;88(1):22-9
18955050
Science. 2001 Nov 2;294(5544):1117-22
11691998
Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4278-83
18586879
Cell Calcium. 1990 Oct;11(9):599-602
2285928
J Comp Neurol. 1981 Apr 1;197(2):271-301
7276236
Anat Rec. 1985 Jun;212(2):199-205
3842042
Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3364-71
17591910
J Comp Neurol. 2005 Apr 11;484(3):331-43
15739235
Adv Exp Med Biol. 2008;613:377-82
18188967
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11020-5
10995468
Proc Natl Acad Sci U S A. 1924 Jul;10(7):329-33
16576828
Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2824-30
17525218
BMC Neurosci. 2006 Jul 13;7:54
16839421
Dev Growth Differ. 2008 May;50(4):253-9
18336580
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9616-9
8415750
J Comp Neurol. 2003 Oct 27;465(4):480-98
12975811
Arch Ophthalmol. 2007 Feb;125(2):151-8
17296890
J Comp Neurol. 2000 Aug 14;424(1):1-23
10888735
J Neurosci. 2004 Mar 17;24(11):2633-42
15028755
Nat Neurosci. 2000 May;3(5):445-51
10769383
J Cell Biol. 1985 Apr;100(4):1284-94
2579958
Hum Mutat. 2001;17(1):42-51
11139241
Nature. 2006 Nov 9;444(7116):203-7
17093405
Vis Neurosci. 1994 May-Jun;11(3):501-17
8038125
Eur J Neurosci. 2005 Sep;22(5):1057-72
16176347
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12156-60
16880381
Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4788-95
16303980
Lancet. 2006 Nov 18;368(9549):1795-809
17113430
Invest Ophthalmol Vis Sci. 1978 Jun;17(6):489-98
659071
Neuron. 2000 Jul;27(1):57-69
10939331
Mol Vis. 2003 Dec 11;9:673-88
14685145
Br J Ophthalmol. 2008 Oct;92(10):1361-8
18662916
Stem Cells. 2007 Oct;25(10):2430-8
17600111
J Neurosci. 2008 Dec 24;28(52):14282-92
19109509
J Comp Neurol. 1974 Jul 1;156(1):81-93
4836656
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6
15210974
J Comp Neurol. 2008 Jan 20;506(3):373-86
18041776
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4188-94
18515565
Neuron. 1999 Jul;23(3):549-57
10433266
Eur J Neurosci. 2007 Nov;26(9):2506-15
17970721
J Comp Neurol. 2004 Jan 26;469(1):70-82
14689473
Nature. 1990 Oct 18;347(6294):677-80
1977087
J Neurosci. 1998 Nov 1;18(21):8648-59
9786972
J Comp Neurol. 2004 Jan 6;468(2):251-63
14648683
J Comp Neurol. 2007 Jan 10;500(2):286-98
17111373
J Comp Neurol. 2009 Feb 1;512(4):453-66
19034952
J Comp Neurol. 2003 May 19;460(1):106-22
12687700
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10139-43
2602362
J Comp Neurol. 2001 Feb 12;430(3):306-20
11169469
J Biol Chem. 1992 Jan 5;267(1):501-7
1309749
Eye (Lond). 2007 Oct;21(10):1352-9
17914439
Neurobiol Aging. 2009 May;30(5):819-28
17920161
J Cell Physiol. 2007 Dec;213(3):809-15
17520694
J Comp Neurol. 2005 Nov 28;492(4):495-509
16228991
Exp Eye Res. 2006 Aug;83(2):367-73
16616739