Incomplete Recovery of Zebrafish Retina Following Cryoinjury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Statement
2.2. Cryoinjury
2.3. Retina Dissection
2.4. Histology
2.5. Progression and the Regression of the Lesion
2.6. Immunofluorescence
2.7. RNA Extraction
2.8. RT-PCR
2.9. RNA Sequencing Library Preparation, Sequencing and Bioinformatics Analysis
3. Results
3.1. Progression of the Induced Lesion with Cryoinjury
3.2. Partial Regeneration Observed by Histology
3.3. Cell Death and Proliferation
3.3.1. Cell Death
3.3.2. Proliferation
3.4. Cellular Components of Residual Defect
3.4.1. Red-Green Double Cones
3.4.2. Rods
3.4.3. Horizontal Cells
3.4.4. Müller Glia (MG)
3.5. Modulation of Transcript Levels during the Degeneration, Proliferation and Regeneration Processes
3.6. RNA Sequencing Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ascl1a | achaete–scute homolog 1 |
CMZ | ciliary marginal zone |
CNS | central nervous system |
cxcr5 | C-X-C chemokine receptor type 5 |
dpi | days post injury |
ECM | extracellular matrix |
FC | fold change |
FDR | false discovery rate |
gata3 | transcription factor GATA-3 |
GCL | ganglion cell layer |
GFAP | glial fibrillary acidic protein |
GFP | green fluorescent protein |
H & E | hematoxylin and eosin |
ILM | inner limiting membrane |
INL | inner nuclear layer |
IPL | inner plexiform layer |
MG | Müller glia |
mmp2 | matrix metalloproteinase-2 |
mmp9 | matrix metalloproteinase-9 |
OLM | outer limiting membrane |
ONL | outer nuclear layer |
OPL | outer plexiform layer |
PBS | phosphate-buffered saline |
PCNA | proliferating cell nuclear antigen |
RPE | retinal pigment epithelium |
RT-PCR | reverse transcriptase polymerase chain reaction |
SEM | standard error of the mean |
tgfbi | TGF-β induced |
VST | variance stabilization transformation |
wnt4a | wingless-type MMTV integration site family, member 4 |
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GENES | ||||||
Comparison | FDR < 0.05 | FDR < 0.05 and fold change >2 | ||||
ALL | UP | DOWN | ALL | UP | DOWN | |
3 dpi_vs_0 dpi | 12088 | 6507 | 5581 | 6014 | 4157 | 1857 |
7 dpi_vs_0 dpi | 10142 | 5625 | 4517 | 4446 | 3682 | 764 |
30 dpi_vs_0 dpi | 2939 | 2489 | 450 | 1500 | 1481 | 19 |
ISOFORMS | ||||||
Comparison | FDR < 0.05 | FDR < 0.05 and fold change >2 | ||||
ALL | UP | DOWN | ALL | UP | DOWN | |
3 dpi_vs_0 dpi | 13362 | 7979 | 5383 | 7655 | 5645 | 2010 |
7 dpi_vs_0 dpi | 10228 | 6343 | 3885 | 5454 | 4562 | 892 |
30 dpi_vs_0 dpi | 2476 | 2205 | 271 | 1673 | 1529 | 144 |
DEG Cluster * | Annotation Cluster ** | Enrichment Score | Category | Term | Gene Count | % of Pathway | Fold Enrichment | p Value *** | |
---|---|---|---|---|---|---|---|---|---|
All significant DEG | 2 | 1 | 12.09 | GOTERM_CC_DIRECT | GO:0005840~ribosome | 34 | 4.21 | 5.59 | 2.71 × 10−13 |
2 | 1 | 12.09 | UP_KEYWORDS | Ribosomal protein | 26 | 3.22 | 6.09 | 1.51 × 10−10 | |
2 | 1 | 12.09 | KEGG_PATHWAY | dre03010:Ribosome | 31 | 3.84 | 4.25 | 1.34 × 10−09 | |
2 | 1 | 12.09 | GOTERM_MF_DIRECT | GO:0003735~structural constituent of ribosome | 31 | 3.84 | 4.21 | 3.49 × 10−08 | |
2 | 2 | 4.44 | INTERPRO | IPR002194:Chaperonin TCP-1, conserved site | 6 | 0.74 | 21.61 | 3.39 × 10−3 | |
2 | 2 | 4.44 | INTERPRO | IPR027410:TCP-1-like chaperonin intermediate domain | 6 | 0.74 | 19.21 | 7.39 × 10−3 | |
2 | 2 | 4.44 | INTERPRO | IPR017998:Chaperone tailless complex polypeptide 1 (TCP-1) | 6 | 0.74 | 19.21 | 7.39 × 10−3 | |
2 | 2 | 4.44 | INTERPRO | IPR027409:GroEL-like apical domain | 6 | 0.74 | 14.41 | 4.18 × 10−2 | |
2 | 2 | 4.44 | INTERPRO | IPR027413:GroEL-like equatorial domain | 6 | 0.74 | 14.41 | 4.18 × 10−2 | |
2 | 3 | 3.55 | INTERPRO | IPR019821:Kinesin, motor region, conserved site | 10 | 1.24 | 6.26 | 3.16 × 10−2 | |
2 | 3 | 3.55 | SMART | SM00129:KISc | 10 | 1.24 | 5.96 | 1.00 × 10−2 | |
3 | 1 | 26.82 | GOTERM_CC_DIRECT | GO:0005840~ribosome | 42 | 8.55 | 11.27 | 2.72 × 10−29 | |
3 | 1 | 26.82 | KEGG_PATHWAY | dre03010:Ribosome | 40 | 8.15 | 11.13 | 1.72 × 10−29 | |
3 | 1 | 26.82 | UP_KEYWORDS | Ribosomal protein | 36 | 7.33 | 13.91 | 9.08 × 10−28 | |
3 | 1 | 26.82 | GOTERM_MF_DIRECT | GO:0003735~structural constituent of ribosome | 40 | 8.15 | 8.59 | 1.43 × 10−22 | |
3 | 1 | 26.82 | UP_KEYWORDS | Ribonucleoprotein | 37 | 7.54 | 9.3 | 5.58 × 10−22 | |
3 | 1 | 26.82 | GOTERM_CC_DIRECT | GO:0030529~intracellular ribonucleoprotein complex | 38 | 7.74 | 8.26 | 3.91 × 10−21 | |
3 | 2 | 3.55 | GOTERM_CC_DIRECT | GO:0005852~eukaryotic translation initiation factor 3 complex | 6 | 1.22 | 14.48 | 5.29 × 10−3 | |
3 | 2 | 3.55 | GOTERM_CC_DIRECT | GO:0016282~eukaryotic 43S preinitiation complex | 5 | 1.02 | 13.58 | 4.98 × 10−2 | |
3 | 3 | 3.41 | GOTERM_CC_DIRECT | GO:0005852~eukaryotic translation initiation factor 3 complex | 6 | 1.22 | 14.48 | 5.29 × 10−3 | |
4 | 2 | 1.98 | PIR_SUPERFAMILY | PIRSF002285:Op18/stathmin | 3 | 1.2 | 40.88 | 2.97 × 10−2 | |
5 | 1 | 8.29 | INTERPRO | IPR008160:Collagen triple helix repeat | 11 | 7.14 | 17.24 | 2.58 × 10−7 | |
5 | 1 | 8.29 | UP_KEYWORDS | Collagen | 9 | 5.84 | 20.41 | 1.06 × 10−6 | |
5 | 1 | 8.29 | GOTERM_CC_DIRECT | GO:0005581~collagen trimer | 9 | 5.84 | 20.13 | 5.32 × 10−7 | |
8 | 1 | 3.51 | GOTERM_BP_DIRECT | GO:0019882~antigen processing and presentation | 5 | 9.43 | 38.96 | 4.36 × 10−4 | |
DEG significant at all timepoints | 1 | 1 | 5.57 | UP_KEYWORDS | Mitosis | 6 | 10.34 | 38.18 | 2.83 × 10−5 |
1 | 1 | 5.57 | UP_KEYWORDS | Cell division | 6 | 10.34 | 24.40 | 2.63 × 10−4 | |
1 | 1 | 5.57 | GOTERM_BP_DIRECT | GO:0007067~mitotic nuclear division | 6 | 10.34 | 20.46 | 1.69 × 10−3 | |
1 | 2 | 3.33 | UP_KEYWORDS | Proteasome | 4 | 6.90 | 29.22 | 2.00 × 10−2 | |
1 | 2 | 3.33 | GOTERM_CC_DIRECT | GO:0000502~proteasome complex | 4 | 6.90 | 25.14 | 2.07 × 10−2 | |
1 | 2 | 3.33 | KEGG_PATHWAY | dre03050:Proteasome | 4 | 6.90 | 21.84 | 1.04 × 10−2 | |
1 | 3 | 3.18 | INTERPRO | IPR019821:Kinesin, motor region, conserved site | 4 | 6.90 | 33.66 | 3.28 × 10−2 | |
1 | 3 | 3.18 | SMART | SM00129:KISc | 4 | 6.90 | 29.22 | 1.03 × 10−2 | |
1 | 3 | 3.18 | INTERPRO | IPR001752:Kinesin, motor domain | 4 | 6.90 | 29.22 | 4.96 × 10−2 | |
1 | 3 | 3.18 | GOTERM_CC_DIRECT | GO:0005871~kinesin complex | 4 | 6.90 | 23.43 | 2.54 × 10−2 | |
1 | 4 | 3.00 | INTERPRO | IPR018525:Mini-chromosome maintenance, conserved site | 3 | 5.17 | 129.05 | 3.40 × 10−2 | |
1 | 4 | 3.00 | SMART | SM00350:MCM | 3 | 5.17 | 113.97 | 9.46 × 10−3 | |
1 | 4 | 3.00 | INTERPRO | IPR001208:Mini-chromosome maintenance, DNA-dependent ATPase | 3 | 5.17 | 116.14 | 4.23 × 10−2 | |
1 | 4 | 3.00 | GOTERM_CC_DIRECT | GO:0042555~MCM complex | 3 | 5.17 | 94.26 | 1.76 × 10−2 | |
1 | 4 | 3.00 | GOTERM_MF_DIRECT | GO:0003678~DNA helicase activity | 3 | 5.17 | 84.78 | 3.33 × 10−2 | |
1 | 5 | 2.73 | INTERPRO | IPR000243:Peptidase T1A, proteasome beta-subunit | 3 | 5.17 | 116.14 | 4.23 × 10−2 |
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Džulová, D.; Lawless, D.; Pinton, G.G.; Renner, N.A.; Schorderet, D.F. Incomplete Recovery of Zebrafish Retina Following Cryoinjury. Cells 2022, 11, 1373. https://doi.org/10.3390/cells11081373
Džulová D, Lawless D, Pinton GG, Renner NA, Schorderet DF. Incomplete Recovery of Zebrafish Retina Following Cryoinjury. Cells. 2022; 11(8):1373. https://doi.org/10.3390/cells11081373
Chicago/Turabian StyleDžulová, Denisa, Dylan Lawless, Gaëtan G. Pinton, Nicole A. Renner, and Daniel F. Schorderet. 2022. "Incomplete Recovery of Zebrafish Retina Following Cryoinjury" Cells 11, no. 8: 1373. https://doi.org/10.3390/cells11081373
APA StyleDžulová, D., Lawless, D., Pinton, G. G., Renner, N. A., & Schorderet, D. F. (2022). Incomplete Recovery of Zebrafish Retina Following Cryoinjury. Cells, 11(8), 1373. https://doi.org/10.3390/cells11081373