title: αA-crystallin in the pathogenesis and intervention of experimental murine corneal neovascularization.
abstract: This study was to determine the potential roles of lens crystallins in the pathogenesis of corneal neovascularization (CorNV) and implications in therapy of CorNV-related diseases. Suture- or chemical burn-induced CorNV in different strains of mice were used. Changes of gene expression patterns were analyzed by microarray, and the results of interesting genes were confirmed by real-time quantitative PCR and Western blot. Mice deficient in αA-crystallin gene were used to evaluate the role of αA-crystallin in the development of CorNV. In some animals, exogenous αA-crystallin proteins were injected around time of CorNV induction. CorNV was assessed by slit-lamp, flat-mounts and histology. In BALB/C mice, the expression of α-, β-, and γ-crystallins were up-regulated at day 5 and returned to baseline level at day 10 of suture-induced CorNV, but remained up-regulated from day 6 to day 14 of chemical burn-induced CorNV. In chemical burn-induced CorNV in C57BL/6J mice, however, they were down-regulated at day 6. Corneal crystallins were down-regulated in both CorNV models at all time points in both BALB/c and C57BL/6J mice. Comparison of CorNV development in αA-crystallin-deficient mice and that in wild-type mice revealed no significant difference. Subconjunctival injection of αA-crystallin significantly attenuated suture-induced CorNV, and the inhibitory activity might be implemented by the increased expression of soluble VEGFR-1. In conclusion, the expression patterns of lens crystallins were time- and strain-dependent but different from that of corneal crystallins in mouse CorNV models. Exogenous αA-crystallin protein attenuated CorNV, potentially by increasing the expression of soluble VEGFR-1.
authors.affiliation: QDU-SEI Joint Ophthalmology Program, Qingdao University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Xia
authors.initials: X
authors.lastname: Qi
authors.forename: Shengwei
authors.initials: S
authors.lastname: Ren
authors.forename: Changkai
authors.initials: C
authors.lastname: Jia
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Song
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016510:Corneal Neovascularization / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D056965:Injections, Intraocular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D038202:alpha-Crystallin A Chain / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D038202:alpha-Crystallin A Chain; D040281:Vascular Endothelial Growth Factor Receptor-1