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[All-trans-retinol (atR) inhibits expression of the metalloproteinase stromelysin in retinal pigment epithelium
1Augenklinik der Ludwig Maximilians Universität München. cschoenf@ak-i.med.uni-muenchen.de
Background:
The pathobiology in proliferative vitreoretinopathy (PVR) is complex. The mechanism of the release of retinal cells from their cellular bond is unknown. The metalloproteinase stromelysin cleaves proteins of the extracellular matrix (ECM). This may liberate retinal cells. The expression of stromelysin in human RPE cells has been demonstrated. Here, stromelysin gene expression under all-trans-Retinal (atR) was investigated.
Materials And Methods:
Human RPE-cells were used from passage 2 to 5. The expression of the human stromelysin gene was determined by reverse transcriptase-polymerase chain reaction using specific oligonucleotides. RPE-cells were incubated with 162 nmol/l tetraphorbolester (TPA) alone or simultaneous with 1 mumol/l atR.
Results:
TPA increased the expression of stromelysin in RPE cells. Incubation with TPA and atR lowered this increase. The decrease of expression was calculated semiquantitatively.
Conclusions:
The expression of stromelysin in RPE cells is lowered after incubation with 1 mumol/l atR. The dedifferentiation of RPE-cells may decrease intracellular atR levels. This could turn an inhibition of stromelysin gene expression to an increase. This may then release retinal cells from their cellular bond and therefore be one of the initial steps in the development of PVR.
Insights
All-trans-Retinal (atR) reduces stromelysin gene expression in retinal pigment epithelial cells. This finding may explain how retinal cells detach, contributing to proliferative vitreoretinopathy (PVR) development.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Context:
- Proliferative vitreoretinopathy (PVR) is a complex condition involving retinal cell detachment.
- The precise mechanisms leading to retinal cell release remain unclear.
- Stromelysin, a matrix metalloproteinase, degrades extracellular matrix (ECM) proteins, potentially liberating retinal cells.
Purpose:
- To investigate the effect of all-trans-Retinal (atR) on stromelysin gene expression in human retinal pigment epithelial (RPE) cells.
- To determine if atR modulates the expression of stromelysin, an enzyme implicated in ECM degradation.
Summary:
- Human RPE cells were cultured and treated with tetraphorbolester (TPA) alone or in combination with atR.
- Reverse transcriptase-polymerase chain reaction was used to quantify stromelysin gene expression.
- TPA significantly increased stromelysin expression, while co-incubation with atR attenuated this increase.
Impact:
- atR significantly lowers stromelysin gene expression in RPE cells.
- This downregulation suggests a potential inhibitory role of atR in the early stages of PVR.
- Understanding this mechanism could lead to novel therapeutic strategies for PVR by targeting RPE cell dedifferentiation and ECM remodeling.
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