Interleukin-6 as a photoreceptor neuroprotectant in an experimental model of retinal detachment
Deborah Chong 1,
Christopher S Boehlke 1,
Qiong-Duan Zheng 2,
Linda Zhang 2,
Ying Han 2,
and
David N. Zacks 2*
1 Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States
2 University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
* To whom correspondence should be addressed. E-mail: davzacks{at}umich.edu.
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Abstract |
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PURPOSE: To test the hypothesis that interleukin-6 (IL-6) prevents photoreceptor cell death during periods of retinal separation from the retinal pigment epithelium (RPE).
METHODS: Retinal-RPE separation was created in wildtype 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 specified times afterwards. 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(+) staining at three days after retinal-RPE separation. At 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 as compared to controls. Gain of IL-6 function through the addition of exogenous IL-6 resulted in significantly increased ONL counts at one month, but not at two months. Re-injection of IL-6 at one month led to continued preservation of ONL counts as compared to controls. A window of opportunity for treatment was detected, as delaying injection of exogenous IL-6 to two weeks after retinal-RPE separation still resulted in significantly greater ONL cell counts as compared to controls.
CONCLUSIONS: IL-6 may serve as a photoreceptor neuroprotectant in the setting of retinal-RPE separation.
Key Words:
apoptosis, retinal detachment, interleukin
