Expression of growth factor mRNA in rabbit PVR model systems
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S R Planck1, J Andresevic, J C Chen
1Department of Ophthalmology, Casey Eye Institute, Oregon Health Sciences University, Portland 97201-4197.
Abstract:
Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
A new rabbit model for proliferative vitreoretinopathy (PVR) was developed using monocytes and a surgical incision. This model mimics human PVR membranes and aids in studying disease mechanisms and treatments.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Proliferative vitreoretinopathy (PVR) causes vision loss due to fibrocellular membrane formation and retinal detachment.
- Current understanding of PVR pathogenesis is limited by the lack of suitable experimental models.
- Identifying key molecular mediators is crucial for developing effective PVR treatments.
Purpose of the Study:
- To establish a reproducible animal model for studying proliferative vitreoretinopathy (PVR).
- To investigate the cellular and molecular mechanisms underlying PVR membrane formation.
- To analyze cytokine expression in experimentally induced PVR.
Main Methods:
- Intravitreal injection of monocytes and a trans-scleral incision in rabbit eyes to induce PVR-like disease.
- Histological analysis of epiretinal membranes to compare with human PVR.
- Northern blot analysis to detect mRNA expression of growth factors (e.g., aFGF, bFGF, PDGF-B, TGF-β) in induced membranes.
Main Results:
- Intravitreal monocytes combined with a surgical incision reliably induced PVR-like disease in rabbits.
- The severity of PVR correlated with the number of monocytes injected.
- Induced epiretinal membranes contained macrophages, epithelial cells, and fibroblast-like cells, similar to human PVR.
- mRNA for acidic fibroblast growth factor (aFGF) was detected in rabbit PVR membranes, but not in injected monocytes.
- aFGF, bFGF, PDGF-B, and TGF-β mRNAs were found in membranes induced by scleral incision and cryopexy.
Conclusions:
- The developed rabbit model effectively replicates key features of human proliferative vitreoretinopathy (PVR).
- Monocytes play a critical role in the formation of PVR membranes.
- The model allows for the investigation of growth factor involvement, such as FGF, PDGF, and TGF-β, in PVR pathogenesis.