Insulin, insulin-like growth factor–1, insulin receptor, and insulin-like growth factor–1 receptor expression in the chick eye and their regulation with imposed myopic or hyperopic defocus

摘要

Purpose: Insulin stimulates eye growthin chicks and this effect is greatly enhanced if the retinal image isdegraded by the defocus of either sign. However, it is unclear whetherthe insulin receptor (IR) is expressed at all in the chicken retina inanimals 1–2 weeks post-hatching. We have investigated IR expression andwhether IR transcript abundance varies in the fundal layers. Toelucidate the possible role of insulin and insulin-like growth factor(IGF)-1 signaling in eye growth regulation, mRNA (mRNA) levels weremeasured for insulin, IGF-1, IR, and IGF-1 receptor (IGF-1R) duringimposed negative or positive defocus. Methods: Chicks were treated binocularlywith positive or negative spectacle lenses for 4 or 24 h, or theyremained untreated (n=6, for each treatment group). Northern blotanalyses were performed to screen for transcription variants in thedifferent fundal layers of untreated animals. Real-time PCR was used toquantify IR, IGF-1R, IGF-1, and insulin mRNAlevels in the different fundal layers of the chick eye in the threetreatment groups. Results: IR mRNA was found in allthe studied tissues, although there is evidence of tissue-specifictranscript variations. Three major transcripts were detected for IR.Thebrain,retina,andchoroid showed the longest transcript (4.3 kb),which was not present in the liver. Nevertheless, the liver and brainshowed a second transcript (2.6 kb) not present in the retina andchoroid. A short transcript (1.3 kb) was the predominant form in theliver and choroid, and it seems to be present in the retinal pigmentepithelium (RPE) and sclera as well. In the retina, no significant geneexpression changes were found when defocus was imposed. Interestingly,in the RPE, both IR and IGF-1R were alreadydownregulated after short periods (4 h) of positive lens wear. Incontrast, IR and IGF-1R were upregulated in the choroidand fibrous sclera during treatment with negative, but not positive,lenses. Conclusions: Differences observed in theIR transcript length in different tissues suggest possiblydifferent functions. The differential regulation of IR and IGF-1Rin the RPE, choroid, and fibrous sclera is consistent with theirinvolvement in a signaling cascade for emmetropization.