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J Song, YG Lee, J Houston, WM Petroll, S Chakravarti, HD Cavanagh, JV Jester; Neonatal Corneal Stromal Development in the Normal and Lumican Knockout Mouse . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1694.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent studies have shown that lumican deficiency produces fusion of stromal collagen fibrils leading to irregularities in collagen fiber spacing and size, thinned corneal stroma and increased light scattering and corneal haze in the lumican knockout mouse. The purpose of this study was to establish the temporal changes in the cornea as related to light scattering, transparency, and stromal development in the lumican knockout mouse. Methods: Lumican knockout mice and CD1 normal mice were evaluated by in vivo confocal microscopy at various times from 1 day to 3 months after birth to quantitatively measure stromal and epithelial thickness and corneal light scattering. Animals were then sacrificed and the density of stromal keratocytes determined by laser scanning confocal microscopy. Results: In the normal neonatal mouse, corneas were translucent at birth and rapidly developed transparency during the first 20 days of life with light scattering measurements of 3761 382 U at day 7 compared to 2225 236 U at day 21. In the lumican knockout, corneas were also translucent at birth and began to develop transparency up to day 14 with decreasing light scattering from 4020 326 U at day 7 to 2793 475 U at day 14. However, light scattering abruptly increased by day 21 (3167 871 U) and remained significantly elevated above the normal cornea to 3 months after birth. While no differences were noted in the epithelial thickness, changes in the stromal thickness were markedly different. In the normal mouse the cornea was thin at birth (64.9 6.2 µm) increasing abruptly to 86.7 10.2 µm at day 14 then decreasing to 66.9 7.5 µm by day 20 and slowly reached adult thickness by 2 months of age (87.7 4.3 µm). By contrast the stroma remained thin after birth in the lumican knockout (60.4 4.6 µm at day 7) and appeared to decrease markedly by day 21 to 50.7 8.4 µm and then remained constant. Although the total number of keratocytes was the same, there was an increase in cell density in the knockout mouse due to the decrease in stromal thickness as compared to the wild type. Conclusion: Lumican deficiency in the neonatal cornea appeared to block the normal swelling or growth of the stroma at day 12-14 (eyelid opening), leading to increased light scattering without affecting keratocyte number. The cause of this swelling in the normal cornea remains unknown.
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