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[Influence of disulfiram on the expression of transforming growth factor-beta2 in form-deprived eyes in chicks]
1Peking University Eye Center, Peking University Third Hospital, Beijing, China.
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.
Conclusion:
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.
Insights
Form-deprived myopia in chicks involves decreased transforming growth factor-beta2 (TGF-beta2) expression. Disulfiram, an inhibitor of retinoid acid synthesis, may suppress myopia by up-regulating TGF-beta2 mRNA.
Area of Science:
- Ophthalmology
- Molecular Biology
- Developmental Biology
Context:
- Myopia, a prevalent vision disorder, is influenced by genetic and environmental factors.
- Form-deprived myopia (FDM) in animal models provides insights into myopia development.
- Transforming growth factor-beta2 (TGF-beta2) plays a role in ocular development and disease.
Purpose:
- To investigate the temporal expression of TGF-beta2 in chick FDM.
- To evaluate the effect of disulfiram (DSF), a retinoid acid (RA) synthesis inhibitor, on refractive development and TGF-beta2 expression in FDM.
Summary:
- FDM in chicks led to myopia and reduced TGF-beta2 expression.
- Disulfiram treatment upregulated TGF-beta2 mRNA in the posterior retinal-choroid.
- Disulfiram inhibited axial elongation and refractive error in FDM eyes.
Impact:
- Disulfiram may offer a therapeutic strategy for myopia by modulating TGF-beta2.
- Understanding TGF-beta2's role in myopia progression can lead to novel treatments.
- This study highlights the link between RA synthesis, TGF-beta2, and refractive development.
