Neonatal corneal stromal development in the normal and lumican-deficient mouse.
OBJECTIVE
The purpose of this study was to characterize temporally stromal growth and transparency in lumican-deficient and normal neonatal mice.


METHODS
Lumican-deficient mice and CD1 wild-type mice were evaluated by in vivo confocal microscopy through-focusing (CMTF) to quantify stromal and epithelial thickness and corneal light-scattering and by laser scanning CM to determine density of keratocytes from 1 day to 12 weeks after birth.


RESULTS
CD1 corneas showed a rapid loss of light-scattering, decreasing by 50% from day 1 to day 12, that paralleled a 60% decrease in density of keratocytes. By contrast, the stroma demonstrated a marked swelling from day 8 to day 12, followed by thinning at day 14. Compared to corneas from CD1 mice, lumican-deficient corneas showed significantly increased (P < 0.05) light-scattering beginning at week 3 that remained elevated above wild-type levels for the duration of the study. Stromal development was also markedly altered, with thinning detected at week 3, followed by no detectable stromal growth for the duration of the study. Density of keratocytes was significantly increased, but the total cell number was similar compared with that in the wild-type cornea, suggesting no effect on keratocyte differentiation.


CONCLUSIONS
Development of normal neonatal corneal transparency appears related to changes in density of keratocytes. The stroma, however, undergoes a marked swelling and thinning at the time of eyelid opening (days 8-14). In the lumican-deficient mouse, stromal swelling is abolished, indicating that this critical phase in stromal development is lumican dependent and essential for normal stromal growth and maintenance of stromal transparency.
Song
Julia
J
Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
Lee
Young-Ghee
YG
Houston
Jennifer
J
Petroll
W Matthew
WM
Chakravarti
Shukti
S
Cavanagh
H Dwight
HD
Jester
James V
JV
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D011508:Chondroitin Sulfate Proteoglycans / Q000172:deficiency*; D003318:Corneal Opacity / Q000378:metabolism / Q000473:pathology*; D003319:Corneal Stroma / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D007632:Keratan Sulfate / Q000172:deficiency*; D008027:Light; D000071234:Lumican; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D012542:Scattering, Radiation
D011508:Chondroitin Sulfate Proteoglycans; C000604307:Lum protein, mouse; D000071234:Lumican; D007632:Keratan Sulfate