Journal: Investigative Ophthalmology & Visual Science
Article Title: Protective Effects of Estradiol on Disease Progression in a Murine Model of Fuchs Endothelial Corneal Dystrophy
doi: 10.1167/iovs.66.15.64
Figure Lengend Snippet: In vivo estradiol (E2) treatment ameliorates the corneal endothelial phenotype in an FECD mouse model. ( A ) Effects of E2 on the corneal endothelial phenotype were investigated in Col8a2 Q455K/Q455K mice, a mouse model of FECD, by supplying E2-supplemented drinking water ad libitum. Representative specular microscopy images of the corneal endothelium from the wild-type, FECD, and FECD + E2 groups. FECD mice exhibited extensive guttae formation and enlarged endothelial cells compared to wild-type mice. E2 treatment reduced guttae formation and maintained smaller endothelial cells with a higher cell density compared with untreated FECD mice. ( B ) Quantification of guttae formation in the wild-type ( n = 9), FECD ( n = 11), and FECD + E2 ( n = 12) groups. The percentage of guttae area was significantly lower in the FECD + E2 group (0.55 ± 0.23%) compared with the FECD group (0.97 ± 0.22%, P < 0.001). ( C ) Quantification of endothelial cell density (ECD). The FECD + E2 group maintained a significantly higher endothelial cell density (2,263 ± 177 cells/mm²) compared with the FECD group (2058 ± 118 cells/mm²; P = 0.004). ( D, E ) A sex-stratified analysis shows that E2 administration significantly reduced the percentage of guttae area in both male mice ( D ; FECD, n = 6; FECD + E2, n = 6; P = 0.002) and female mice ( E ; FECD, n = 5; FECD + E2, n = 6; P = 0.018) compared with their respective untreated controls. ( F, G ) Similarly, the analysis of endothelial cell density, stratified by sex, shows that E2 treatment resulted in a significantly higher density in both male mice ( F ; FECD, n = 6; FECD + E2, n = 6; P = 0.049) and female mice ( G ; FECD, n = 5; FECD + E2, n = 6; P = 0.013). ( H, I ) Quantitative PCR analysis shows that the expression of the ECM-related genes FN1 ( H ) and COL1A1 ( I ), which was elevated in the FECD group, was significantly suppressed by E2 administration. ( J ) Immunofluorescence for fibronectin ( green ) revealed minimal deposition in wild-type corneas, whereas its accumulation was evident in the corneas of FECD model mice. This pathological deposition was markedly suppressed following E2 treatment. Nuclei were counterstained with DAPI ( blue ). Images are representative of four independent experiments. Scale bar = 100 µm.
Article Snippet: The TaqMan primers used were GAPDH , Hs00266705_mL; FN1 , Hs00365052_mL; BGN , Hs00959143_mL; and COL1A1 , Hs00164004_mL (Applied Biosystems).
Techniques: In Vivo, Microscopy, Real-time Polymerase Chain Reaction, Expressing, Immunofluorescence
Proteintech is a verified supplier 
