Neurotrophins such as CNTF have been shown to be efficacious therapeutic molecules that slow the progression of retinal degeneration. Previous studies have shown that administration of exogenous CNTF to the retina promotes survival of both the photoreceptors
22 26 27 in retinal degeneration models and the cells of the inner retina
28 29 in optic nerve injury models, most likely through upregulation of the Bcl-xL family of antiapoptotic proteins.
30 31 Although the CNTF receptor has been localized to the outer segments of the photoreceptors,
32 the mechanism of CNTF neuroprotection to the photoreceptors may be indirectly mediated through Müller cells.
33 34 35 Whether CNTF is neuroprotective to the photoreceptors through a direct or indirect mechanism, it remains an effective neuroprotectant among multiple neuronal populations, across many species of animal neurodegenerative models.
21 22 36 Our study demonstrates that prolonged, intravitreous administration of CNTF lowered the current thresholds needed for electrical stimulation of the retina in RCS rats as measured by EECPs. Retinal sensitivity to electrical stimulation was significantly enhanced in 10-ng/d CNTF-treated eyes when compared with untreated eyes and all other treatment groups
(Fig. 8) . The CNTF-induced preservation of retinal sensitivity allowed for more desirable stimulation parameters, with lower electrical currents needed to bring cells to the threshold. Similar results were reported with chronic administration of CNTF and BDNF to chemically deafened animals with cochlear implants.
36 Neurotrophic intervention with a cochlear implant resulted in decreased stimulation thresholds and an increased density of spiral ganglion cells, allowing the cochlear implants to be much more effective. It is important to note that while we delivered electrical current to evaluate retinal sensitivity, we did not use the stimulation parameters employed by others to effect neuroprotection.
13 14 Although it is possible that the electrical stimulation we used to elicit EECPs conferred a degree of neuroprotection on the degenerating retina, it is unlikely, because the short duration of stimulation used and the 4-week interval between EECP threshold measurements.