CNTF, a key factor mediating the beneficial effects of inflammatory reactions in the eye

Abstract

Sir, retinal ganglion cells (RGCs) are normally unable to regenerate axons. However, they can be transformed into a robust regenerative state by lens injury (LI) or by intravitreal injections of either lens-derived β-/γ-crystallins or zymosan (Fischer et al ., 2000, 2001, 2004, 2008; Leon et al ., 2000). Based on evidence provided in Muller et al . (2007) and the literature, we propose that astrocyte-derived CNTF and activation of its major downstream signalling pathway in RGCs, the JAK/STAT3 pathway, are both essentially involved in switching these neurons to an active regenerative state after LI. By arguing against a role of CNTF and JAK/STAT3 signalling in this context, Benowitz and colleagues have ignored important evidence in the literature and also presented data from our own and other groups inaccurately, as described later. The literature contains compelling evidence that CNTF directly stimulates axon regeneration of RGCs. For instance, using purified (immunopanned) RGCs, Lingor et al . (2008) have recently demonstrated that CNTF stimulates axon outgrowth of primary RGCs without requiring the elevation of cAMP. Benowitz and colleagues ignore this important piece of evidence, instead only mentioning the significant, but less-pronounced effects of CNTF on RGC-5 cells shown in the same paper (Lingor et al ., 2008). However, RGC-5 cells are not primary neurons but rather a transformed RGC cell line derived from animals at postnatal day 1 (Krishnamoorthy et al ., 2001). For this reason, the reported stronger effects on primary RGCs are much more relevant for assessing the neuritogenic potency of CNTF. Other papers provide further evidence that CNTF stimulates axon outgrowth of postnatal and adult RGCs in culture without requiring cAMP elevation (Lorber et al ., 2002, 2007). Consistent with these, we have also found that CNTF highly significantly stimulates axon regeneration of adult RGCs …