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Forskolin modifies retinal vascular development in Mrp4-knockout mice
Wataru Matsumiya1, Sentaro Kusuhara, Keiko Hayashibe
1Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Investigative Ophthalmology & Visual Science
|November 17, 2012
Summary
Multidrug resistance protein 4 (MRP4) normally supports retinal vascular development. Loss of MRP4 function suppressed vascular growth when cAMP levels were artificially increased, suggesting a protective role.
Area of Science:
- Ophthalmology
- Vascular Biology
- Molecular Biology
Background:
- Multidrug resistance protein 4 (MRP4) is expressed in retinal vascular endothelial cells (ECs) and effluxes cyclic adenosine monophosphate (cAMP).
- MRP4's role in retinal vascular development is not fully understood.
Purpose of the Study:
- To investigate the function of MRP4 in the development of retinal vasculature.
- To determine if MRP4 influences retinal vascular growth by regulating intracellular cAMP levels.
Main Methods:
- Retinal vascularization in Mrp4(-/-) mice was assessed using whole-mount immunohistochemistry.
- Mice were treated with forskolin (a cAMP inducer) or exposed to hyperoxia to evaluate vascular formation, cell proliferation, apoptosis, and pericyte coverage.
Main Results:
- Mrp4(-/-) mice showed suppressed retinal vascular development, reduced vascularization, and inhibited tip cell formation when treated with forskolin.
- Forskolin-induced treatment in Mrp4(-/-) mice led to increased EC proliferation and apoptosis, decreased pericyte coverage, and more "empty sleeves."
- Mrp4(-/-) mice exhibited increased avascular areas under hyperoxic conditions.
Conclusions:
- MRP4 plays a protective role in retinal vascular development.
- Regulating intracellular cAMP levels by MRP4 is crucial for normal retinal vascular growth and stability.
