[Influence of disulfiram on the expression of transforming growth factor-beta2 in form-deprived eyes in chicks].
OBJECTIVE
To explore the temporal expression of retinal-choroidal transforming growth factor-beta2 (TGF-beta2) in form-deprived myopia (FDM) chick eyes and study the effect of an inhibitor (disulfiram, DSF) of retinoid acid (RA) synthesis on refractive development and the expression of TGF-beta2.


METHODS
Ninety new hatched white leghorn chicks were divided randomly and equally into 3 groups: unilateral occluded with frosted goggles (Group A); unilateral intravitreal injection of 4 mmol of the non-specific aldehydedehydrogenase inhibitor disulfiram with further treatment with goggles (Group B); unilateral intravitreal injections of 4 mmol of disulfiram without further treatment with goggles (Group C). Refraction and axial length were measured on 1, 7 and 14 days after treatment. Expression levels of TGF-beta2 and TGF-beta2 mRNA in the retinal-choroid layer were analyzed by immunohistochemistry and real-time RT-PCR.


RESULTS
In Group A, the form-deprived eyes made by goggles developed myopia (P<0.05 on day 1, P<0.01 on days 7 and 14, compared with the contralateral eyes) with a lengthening of the axial length (P<0.01 on days 7 and 14, compared with the contralateral eyes), as well as a lower level of TGF-beta2 expression (P<0.01 on days 7 and 14, compared with the contralateral eyes). In Groups B and C, there was no statistically significant difference in refraction and axial length between treated and contralateral eyes (P>0.05) with TGF-beta2 mRNA level growing on day 7 and decreased on day 14 in group B and decreased on day 1, increased on days 7 and 14 in Group C (P<0.01, compared with the contralateral eyes). Immunohistochemistry showed that the expression of TGF-beta2 was mainly changed in the outer part of photoreceptor layer and retinal pigment epithelium (RPE) layer.


CONCLUSIONS
TGF-beta2 mRNA level decreased in FDM eyes. Disulfiram can up-regulate the level of TGF-beta2 mRNA expression in the posterior retinal-choroid, and inhibit the elongation of axial length and refractive error made by frosted goggles as well. Disulfiram which inhibits the synthesis of retinoid acid may suppress deprivation myopia by up-regulating the expression level of TGF-beta2 mRNA.
Xie
Fang
F
Peking University Eye Center, Peking University Third Hospital, Beijing, China.
Chen
Yue Guo
YG
D000818:Animals; D002645:Chickens; D004221:Disulfiram / Q000494:pharmacology*; D009216:Myopia / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D012160:Retina / Q000378:metabolism; D012683:Sensory Deprivation; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D053781:Transforming Growth Factor beta2; D014212:Tretinoin; D004221:Disulfiram