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Originally published In Press as doi:10.1167/iovs.07-1641 on March 31, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:3193-3200.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1641
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Interleukin-6 as a Photoreceptor Neuroprotectant in an Experimental Model of Retinal Detachment

Deborah Y. Chong, Christopher S. Boehlke, Qiong-Duan Zheng, Linda Zhang, Ying Han, and David N. Zacks

From the Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan.

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.






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