Neuroprotective properties of ciliary neurotrophic factor in the retina for the treatment of macular telangiectasia type 2

Neurotrophic factors are a family of proteins that promote the growth and survival of both developing and mature neurons. Extensive preclinical studies have demonstrated neuroprotective properties conferred by ciliary neurotrophic factor (CNTF) in a variety of neuron types across several species. Neuroprotection that CNTF confers slows or prevents neuron loss and appears to be agnostic to the nature of the neurodegenerative mutation or injury. However, translation of these studies to the clinic remains a challenge due in part to delivery barriers inherent to the central nervous system and the short half-life of CNTF. The molecular effect of CNTF delivered by a variety of strategies in model systems has been extensively studied in the neural retina. Long-term retinal neuroprotection has been documented using encapsulated cells that have been genetically modified to produce a stable source of CNTF. Clinical trials have shown that CNTF is well tolerated for use in the human retina. This review focuses on the mechanism of action of CNTF and its potential as a therapeutic agent in retinal disease, with a focus on macular telangiectasia type 2 where CNTF has shown efficacy in slowing the rate of ellipsoid zone loss. • CNTF has demonstrated neuroprotection in models of retinal degeneration. • CNTF exerts several downstream effects, activating JAK/STAT cell survival pathway. • Encapsulated cells are genetically engineered to produce continual CNTF delivery. • In preclinical animal trials and a large clinical trial, CNTF was safe/effective.