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P. H. Frederikse, J. Foglio, C. Bitel; Brain Specific Micro RNAs and Synaptic Vesicle Protein Machinery in Lenses Are Evolutionarily Conserved Between Vertebrates and Invertebrates. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2014.
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© ARVO (1962-2015); The Authors (2016-present)
The goal of this study is to provide further evidence establishing the fundamental role of basic cell biology and gene regulation mechanisms in lens, which happen to be uniquely shared with neurons, that when subverted by stress or aging contribute to cataractogenesis. Previously, we demonstrated the remarkable extent to which neuronal synaptic vesicle trafficking machinery, centered on the normal role of the Alzheimer precursor protein (APP), also has a fundamental role in lens development and cell biology. More recently, we demonstrated that 'neuron-specific' micro RNAs (miRNAs) with critical roles in brain development are also expressed in the lens. Here, we investigate lens synaptic vesicle cell biology and 'brain-specific' miRNAs in invertebrates to determine if expected evolutionary conservation of these processes has occurred, and to solidify links between synaptic vesicle trafficking and neuronal miRNA gene regulation in lens and brain in order to understand their role in cataractogenesis.
Loligo pealei is a classic invertebrate model used to study neurons and synaptic vesicle transport. Synaptic vesicle proteins, APP, & kinesin motor protein expression and distribution were examined in mammalian and fish lenses and compared with squid lenses using RT-PCR, immunoblot, and immunohistochemistry. ‘Brain-specific’ miRNAs in vertebrate and invertebrate lenses were assayed on northern blots and compared with brain.
The data demonstrate lens expression of synapsin, synaptotagmin, SNAP25, APP, kinesin heavy and light chain in invertebrate lenses, consistent with our previous studies, and with microtubules in vertebrate and invertebrate lenses shown by others. We also demonstrate conserved lens expression of brain-specific miRNAs, including miR-124, miR-7, miR125b, and let-7. miR-124 and synaptic vesicle protein gene expression linked by tumor suppressor REST/NRSF regulation is discussed.
We provide further evidence that basic synaptic vesicle transport machinery and micro RNA regulatory mechanisms that have been shown to also fundamentally characterize neurons, are evolutionarily conserved in the invertebrate lens and brain. Finally, in light of observations that sensory organs pre-date the brain, and that camera eyes with lenses remarkably similar to mammals, are present in jellyfish and dinoflagellates (e.g. Gehring J Hered. 2005;96:171), our results lead us to speculate further that synaptic vesicle transport and miRNA mechanisms that define neurons may have been present first in primitive lenses.
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