PMID- 18378582 OWN - NLM STAT- MEDLINE DCOM- 20080731 LR - 20220408 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 49 IP - 7 DP - 2008 Jul TI - Interleukin-6 as a photoreceptor neuroprotectant in an experimental model of retinal detachment. PG - 3193-200 LID - 10.1167/iovs.07-1641 [doi] AB - PURPOSE: To test the hypothesis that interleukin (IL)-6 prevents photoreceptor cell death during periods of retinal separation from the retinal pigment epithelium (RPE). METHODS: Retinal-RPE separation was created in wild-type C57BL mice, IL-6(-/-) mice, and Brown Norway rats by subretinal injection of 1% hyaluronic acid. In some animals, anti-IL-6 neutralizing antibody (NAB) or exogenous IL-6 was administered into the subretinal space at the time of separation or at specified times afterward. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed 3 days after separation to detect apoptotic photoreceptors. Photoreceptor cell counts were performed after 1 and 2 months. RESULTS: Loss of IL-6 function through genetic ablation (IL-6(-/-) mice) or injection of anti-IL-6 NAB resulted in significantly increased levels of TUNEL-positive staining 3 days after retinal-RPE separation. One month after separation, outer nuclear layer (ONL) cell counts were significantly lower in IL-6(-/-) mice or in animals injected with anti-IL-6 NAB than in controls. Gain of IL-6 function through the addition of exogenous IL-6 resulted in significantly increased ONL counts at 1 month but not at 2 months. Reinjection of IL-6 at 1 month led to continued preservation of ONL counts compared with controls. A window of opportunity for treatment was detected because delaying injection of exogenous IL-6 to 2 weeks after retinal-RPE separation still resulted in significantly greater ONL cell counts compared with controls. CONCLUSIONS: IL-6 may serve as a photoreceptor neuroprotectant in the setting of retinal-RPE separation. FAU - Chong, Deborah Y AU - Chong DY AD - Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105-0714, USA. FAU - Boehlke, Christopher S AU - Boehlke CS FAU - Zheng, Qiong-Duan AU - Zheng QD FAU - Zhang, Linda AU - Zhang L FAU - Han, Ying AU - Han Y FAU - Zacks, David N AU - Zacks DN LA - eng GR - EY-07003/EY/NEI NIH HHS/United States GR - K08-124-14705/PHS HHS/United States GR - F31 EY007003/EY/NEI NIH HHS/United States GR - K08 EY014705/EY/NEI NIH HHS/United States GR - P30 EY007003/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080331 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Antibodies) RN - 0 (Interleukin-6) RN - 0 (Neuroprotective Agents) SB - IM MH - Animals MH - Antibodies/pharmacology MH - Apoptosis/drug effects MH - Cell Count MH - Drug Administration Schedule MH - Humans MH - Interleukin-6/administration & dosage/deficiency/immunology/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neuroprotective Agents/administration & dosage/antagonists & inhibitors/metabolism/*pharmacology MH - Photoreceptor Cells, Vertebrate/*drug effects/metabolism MH - Rats MH - Rats, Inbred BN MH - Retina/drug effects/pathology MH - Retinal Detachment/pathology/*physiopathology MH - Time Factors PMC - PMC3704181 MID - NIHMS488080 EDAT- 2008/04/02 09:00 MHDA- 2008/08/01 09:00 PMCR- 2013/07/08 CRDT- 2008/04/02 09:00 PHST- 2008/04/02 09:00 [pubmed] PHST- 2008/08/01 09:00 [medline] PHST- 2008/04/02 09:00 [entrez] PHST- 2013/07/08 00:00 [pmc-release] AID - iovs.07-1641 [pii] AID - 10.1167/iovs.07-1641 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3193-200. doi: 10.1167/iovs.07-1641. Epub 2008 Mar 31.