LIF-dependent JAK3 activation is not essential for retinal degeneration

Retinal degeneration causes the induction of a leukemia inhibitory factor (LIF)-controlled survival pathway which includes Janus kinase/signal transducer and activator of transcription signaling. Lack of LIF prevents activation of this signaling cascade and accelerates disease progression leading to a fast loss of photoreceptor cells. In this study, we show that expression of Janus kinase 3 (Jak3), but not of the other members of the family of Janus kinases, is induced in four different models of retinal degeneration and that LIF is essential and sufficient to activate Jak3 gene expression. We also show that the induction of Jak3 and Lif may not depend directly on cell death but rather on the retinal stress during photoreceptor degeneration. However, despite its dependence on LIF, JAK3 is not essential for LIF-mediated photoreceptor protection or gene expression. Also, absence of JAK3 in knockout mice did not affect immune-related responses in the degenerating retina. JAK3 may therefore play a different, yet unknown, role in the retinal response to photoreceptor injury.