Department of Ophthalmology and Gene Therapy Center
Amino Acids, Peptides, and Proteins | Cellular and Molecular Physiology | Eye Diseases | Molecular and Cellular Neuroscience | Ophthalmology | Sense Organs
We aimed to investigate fractalkine (CX3CL1) protein expression in wild type (wt) retina and its alterations during retinal degeneration in mouse model (rd10) of retinitis pigmentosa. Forms of retinal protein CX3CL1, total protein and mRNA levels of CX3CL1 were analyzed at postnatal days (P) 5, 10, 14, 22, 30, 45, and 60 by Western blotting and real-time PCR. Cellular sources of CX3CL1 were investigated by in situ hybridization histochemistry (ISH) and using transgenic (CX3CL1cherry) mice. The immunoblots revealed that in both, wt and rd10 retinas, a membrane integrated approximately 100 kDa CX3CL1 form and a cleaved approximately 85 kDa CX3CL1 form were present at P5. At P10, accumulation of another presumably intra-neuronal approximately 95 kDa form and a decrease in the approximately 85-kDa form were observed. From P14, a approximately 95 kDa form became principal in wt retina, while in rd10 retinas a soluble approximately 85 kDa form increased at P45 and P60. In comparison, retinas of rd10 mice had significantly lower levels of total CX3CL1 protein (from P10 onwards) and lower CX3CL1 mRNA levels (from P14), even before the onset of primary rod degeneration. ISH and mCherry reporter fluorescence showed neurons in the inner retina layers as principal sites of CX3CL1 synthesis both in wt and rd10 retinas. In conclusion, our results demonstrate that CX3CL1 has a distinctive course of expression and functional regulation in rd10 retina starting at P10. The biological activity of CX3CL1 is regulated by conversion of a membrane integrated to a soluble form during neurogenesis and in response to pathologic changes in the adult retinal milieu. Viable mature neurons in the inner retina likely exhibit a dynamic intracellular storage depot of CX3CL1.
Neurons, Ganglion cells, Microglial cells, In situ hybridization, Photoreceptors, Probe hybridization, Retina
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DOI of Published Version
PLoS One. 2014 Sep 5;9(9):e106562. doi: 10.1371/journal.pone.0106562. eCollection 2014. Link to article on publisher's site
Zieger M, Ahnelt PK, Uhrin P. (2014). CX3CL1 (fractalkine) protein expression in normal and degenerating mouse retina: in vivo studies. Open Access Articles. https://doi.org/10.1371/journal.pone.0106562. Retrieved from https://escholarship.umassmed.edu/oapubs/2475
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