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Temporal expression of the transthyretin gene in the developing rat eye
R Mizuno1, T Cavallaro, J Herbert
1Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York.
Insights
Transthyretin (TTR) mRNA is found in the rat choroid plexus early in development. In the eye, TTR mRNA expression in the retinal pigment epithelium (RPE) increases postnatally, suggesting differing roles and environmental responsiveness.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Transthyretin (TTR) is a key transport protein synthesized in the liver, choroid plexus (CP), and eye.
- The retinal pigment epithelium (RPE) was recently identified as a specific site of TTR synthesis in the rat eye.
- This finding suggested a functional similarity between the RPE and CP epithelium.
Purpose of the Study:
- To investigate the developmental expression pattern of TTR mRNA in the rat eye and brain.
- To compare the temporal expression of TTR mRNA in the CP and RPE during development.
Main Methods:
- In situ hybridization was used to detect TTR mRNA.
- Quantitative densitometry measured TTR mRNA levels.
- Expression was analyzed from embryonic day 10 (e10) to postnatal day 7 (P7).
Main Results:
- TTR mRNA was abundant in the primordial CP early in development (e10-12).
- In the eye, TTR mRNA was detected at low levels in a subset of RPE cells after organogenesis (e16).
- RPE TTR mRNA levels gradually increased until e21, surged on day P1, and stabilized by P7.
Conclusions:
- The temporal expression patterns suggest distinct developmental roles for TTR in the CP and RPE.
- The postnatal surge in RPE TTR mRNA may be influenced by environmental factors, such as light, after birth.
Abstract:
Transthyretin (TTR) is a 55-kilodalton tetrameric protein that plays an important role in the plasma transport of thyroxine and retinol. Plasma TTR is synthesized in the liver, but major sites of synthesis also have been described in the choroid plexus (CP) epithelium, the visceral yolk sac, and the eye. Recently, the retinal pigment epithelium (RPE) was identified as the specific site of TTR synthesis in the rat eye, and it was suggested that this established a functional homology between the RPE and the CP epithelium. In this study, the temporal pattern of TTR mRNA expression was investigated in the rat eye and brain during development (embryonic day 10 [e10]-postnatal day 7 [P7]) by in situ hybridization and quantitative densitometry. The TTR mRNA was present in abundance in the primordial CP before organogenesis (e10-12), but in the eye, TTR mRNA first was detected at considerably lower levels after organogenesis (e16) and only in a subset of RPE cells in the equatorial region. The relative abundance of TTR mRNA in RPE rose gradually until e21, but on the first day of life a surge was seen, followed by stabilization at adult levels by P7. These findings suggest that the requirement for TTR in CP and RPE, and possibly its function, may differ during development. The postnatal surge in RPE TTR message levels raises the possibility that transcription of the TTR gene in the newborn animal may be responsive to newly encountered environmental stimuli in the perinatal period, such as incident light.