AIM: To investigate the morphological changes and the expression of hypoxia-inducible factor-1 alpha(HIF-1α)subunit during embryonic development of rat lens and explore the role of HIF-1α in lens development process.

METHODS: Thirty clean pregnant Wistar rats were divided into 6 embryon groups,10-d, 12-d, 14-d, 16-d, 18-d and 20-d embryo. Two embryons were randomized obtained from every pregnant rat. One of the eyeball samples that were parallel to sagittal axis of optic nerve were cut into serial sections, used HE staining and examined by light microscope. Expression of HIF-1α protein in lens was detected by immunohistochemistry. The positive expression of HIF-1α mRNA of the other eyeball samples was detected by real-time PCR.

RESULTS:In the 10^th d of embryo(E10), the formation of lens vesicle were recognized under the light microscope. In the 12^th d of embryo(E12), the anteriorly situated cells and posteriorly situated cells have already differentiated. The anteriorly situated cells were epithelium. In the 14^th d of embryo(E14), primary fibers which came from posteriorly situated cells were examined. In the 16^th d of embryo(E16), the lens epithelium undergoes extensive proliferation, and enlongate into the secondary fibers. In the 20^th d of embryo(E20), the lens was maturation. By immunohistochemistry staining, the HIF-1α was highly expressed in the lens embryonic development. The expression was gradually promoting from E10 to E16, then reducing. The lens epithelium expressed more HIF-1α than fibers. The highest mean density was at E16, the lowest at E20. The difference was significant among of the 6 groups(P<0.0001). The E10 group was combined with the E12 group, the E14 group was combined with the E16 group, showing no significant difference(P>0.05). The other groups were compared with each other, finding significant difference(P<0.05). By the real-time PCR, HIF-1α mRNA was highly expressed in the lens development, and was different at different time. The expression of HIF-1α mRNA was increasing from E10 to E16, then descending at E18 and E20. The expression of HIF-1α mRNA was the highest at E16, the lowest at E20. The difference was significant among of the 6 groups(P<0.0001). The E10 group was combined with the E12 group, showing no significant difference(P>0.05). The other groups were compared with each other, finding significant difference(P<0.05).

CONCLUSION:The lens of Wistar rats differentiate from the E10 when the vesicle formed through the embryo phase. The lens is basic mature before birth. The HIF-1α in the lens embryonic development is highly expressed and changeful. The varies of HIF-1α expression is depend upon rat embryo development indicating that HIF-1α might participate in the process of development of rat lens.