TY - JOUR
T1 - αA-crystallin in the pathogenesis and intervention of experimental murine corneal neovascularization
AU - Zhu, Wei
AU - Qi, Xia
AU - Ren, Shengwei
AU - Jia, Changkai
AU - Song, Zicheng
AU - Wang, Yiqiang
N1 - Funding Information:
This work was supported by the National Science Foundation of China ( 30973250 , 81100642 ) and Shandong Natural Science Foundation ( JQ200908 ).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Antiangiogenic compartments
KW - Corneal neovascularization
KW - Lens crystallins
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=84860230383&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2012.03.005
DO - 10.1016/j.exer.2012.03.005
M3 - Article
C2 - 22465406
AN - SCOPUS:84860230383
SN - 0014-4835
VL - 98
SP - 44
EP - 51
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 1
ER -