PMID- 25595590 OWN - NLM STAT- MEDLINE DCOM- 20160810 LR - 20220410 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 12 DP - 2015 Jan 17 TI - Chemokine-mediated inflammation in the degenerating retina is coordinated by Muller cells, activated microglia, and retinal pigment epithelium. PG - 8 LID - 10.1186/s12974-014-0224-1 [doi] LID - 8 AB - BACKGROUND: Monocyte infiltration is involved in the pathogenesis of many retinal degenerative conditions. This process traditionally depends on local expression of chemokines, though the roles of many of these in the degenerating retina are unclear. Here, we investigate expression and in situ localization of the broad chemokine response in a light-induced model of retinal degeneration. METHODS: Sprague-Dawley (SD) rats were exposed to 1,000 lux light damage (LD) for up to 24 hrs. At time points during (1 to 24 hrs) and following (3 and 7 days) exposure, animals were euthanized and retinas processed. Microarray analysis assessed differential expression of chemokines. Some genes were further investigated using polymerase chain reaction (PCR) and in situ hybridization and contrasted with photoreceptor apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Recruitment of retinal CD45 (+) leukocytes was determined via fluorescence activated cell sorting (FACS), and expression of chemokine receptors determined using PCR. RESULTS: Exposure to 24 hrs of LD resulted in differential expression of chemokines including Ccl3, Ccl4, Ccl7, Cxcl1, and Cxcl10. Their upregulation correlated strongly with peak photoreceptor death, at 24 hrs exposure. In situ hybridization revealed that the modulated chemokines were expressed by a combination of Muller cells, activated microglia, and retinal pigment epithelium (RPE). This preceded large increases in the number of CD45(+) cells at 3- and 7-days post exposure, which expressed a corresponding repertoire of chemokine receptors. CONCLUSIONS: Our data indicate that retinal degeneration induces upregulation of a broad chemokine response whose expression is coordinated by Muller cells, microglia, and RPE. The findings inform our understanding of the processes govern the trafficking of leukocytes, which are contributors in the pathology of retinal degenerations. FAU - Rutar, Matt AU - Rutar M AD - John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Canberra, ACT 2601, Australia. matt.rutar@anu.edu.au. AD - ANU Medical School, The Australian National University, 54 Mills Road, Canberra, ACT 2601, Australia. matt.rutar@anu.edu.au. FAU - Natoli, Riccardo AU - Natoli R AD - John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Canberra, ACT 2601, Australia. riccardo.natoli@anu.edu.au. AD - ANU Medical School, The Australian National University, 54 Mills Road, Canberra, ACT 2601, Australia. riccardo.natoli@anu.edu.au. FAU - Chia, R X AU - Chia RX AD - John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Canberra, ACT 2601, Australia. u4957724@anu.edu.au. FAU - Valter, Krisztina AU - Valter K AD - John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Canberra, ACT 2601, Australia. jan.provis@anu.edu.au. AD - ANU Medical School, The Australian National University, 54 Mills Road, Canberra, ACT 2601, Australia. jan.provis@anu.edu.au. FAU - Provis, Jan M AU - Provis JM AD - John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Canberra, ACT 2601, Australia. krisztina.valter-kocsi@anu.edu.au. AD - ANU Medical School, The Australian National University, 54 Mills Road, Canberra, ACT 2601, Australia. krisztina.valter-kocsi@anu.edu.au. LA - eng PT - Journal Article DEP - 20150117 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Chemokines) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Cell Death MH - Chemokines/genetics/*metabolism MH - Disease Models, Animal MH - Ependymoglial Cells/*metabolism MH - Flow Cytometry MH - Gene Expression Regulation/radiation effects MH - Inflammation/*etiology MH - Light/adverse effects MH - Microarray Analysis MH - Microglia/*metabolism MH - Photoreceptor Cells/pathology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Retina/pathology MH - Retinal Degeneration/*complications/etiology/*pathology MH - Retinal Pigment Epithelium/*metabolism MH - Statistics, Nonparametric MH - Time Factors PMC - PMC4308937 EDAT- 2015/01/18 06:00 MHDA- 2016/08/11 06:00 PMCR- 2015/01/17 CRDT- 2015/01/18 06:00 PHST- 2014/10/09 00:00 [received] PHST- 2014/12/18 00:00 [accepted] PHST- 2015/01/18 06:00 [entrez] PHST- 2015/01/18 06:00 [pubmed] PHST- 2016/08/11 06:00 [medline] PHST- 2015/01/17 00:00 [pmc-release] AID - s12974-014-0224-1 [pii] AID - 224 [pii] AID - 10.1186/s12974-014-0224-1 [doi] PST - epublish SO - J Neuroinflammation. 2015 Jan 17;12:8. doi: 10.1186/s12974-014-0224-1.