Interleukin-6 as a photoreceptor neuroprotectant in an experimental model of retinal detachment.
OBJECTIVE
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.
Chong
Deborah Y
DY
Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105-0714, USA.
Boehlke
Christopher S
CS
Zheng
Qiong-Duan
QD
Zhang
Linda
L
Han
Ying
Y
Zacks
David N
DN
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D004334:Drug Administration Schedule; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012163:Retinal Detachment / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D000906:Antibodies; D015850:Interleukin-6; D018696:Neuroprotective Agents