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X Xia; Retinal Degeneration Induced by Lens-specific expression of Oncostatin M . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2716.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Oncostatin M(OSM) is a cytokine released by lymphocytes and macrophages that can function as a growth regulator. A homologue, LIF can inhibit photoreceptor differentiation when expressed in the lens of transgenic mice. In order to test OSM for comparable activity, in this study, we determined the effects of lens-specific overexpression of OSM on the development of eye. Methods: A construct with the truncated mouse OSM cDNA(661bp) linked to the mouse aA-crystallin promoter(CPV2) was used to generate transgenic mice. Mice were characterized by routine histology, in situ hybridization, western blotting and immunohistochemistry. Cell proliferation was analyzed by BrdU incorporation. TUNEL assays were used to detect cell death. Results: Three CPV2-OSM transgenic families were generated. The transgenic mice in each family had cataract and microphthalmia.Expression of the OSM transgene was detected specifically in lens fiber cells. At E17.5 we observed the onset of retinal degeneration in the mid portion of the transgenic retinas. By birth 50% or more of the retinal cells were missing ,leaving large cell-free gaps within the retina. TUNEL assays showed extensive induction of apoptosis.Brdu incorporation indicated that there was no significant difference of neuronal proliferation. Most strikingly, caspase 3 protein expression was induced throughout the transgenic retinas as well as the lens epithelial cells. Conclusion: Lens-specific overexpression of OSM induces caspase 3 expression in retinal cells followed by program cell death.
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